Gene products differentially expressed in cancerous cells

ABSTRACT

The present invention provides polynucleotides, as well as polypeptides encoded thereby, that are differentially expressed in cancer cells. These polynucleotides are useful in a variety of diagnostic and therapeutic methods. The present invention further provides methods of reducing growth of cancer cells. These methods are useful for treating cancer.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of and claims priority to U.S.application Ser. No. 10/948,737, filed Sep. 22, 2004, which iscontinuation-in-part of and claims priority to U.S. application Ser. No.10/616,900, filed on Jul. 9, 2003, which is a continuation of U.S.application Ser. No. 09/872,850, filed on Jun. 1, 2001, now abandoned,which claims the benefit of U.S. provisional application Ser. No.60/208,871, filed on Jun. 2, 2000. U.S. application Ser. No. 10/948,737is a continuation-in-part of and claims priority to U.S. applicationSer. No. 10/081,519, filed on Feb. 21, 2002, now abandoned, which claimsthe benefit of U.S. provisional application Ser. No. 60/270,959, filedon Feb. 21, 2001. U.S. application Ser. No. 10/948,737 is also acontinuation-in-part of and claims priority to U.S. application Ser. No.10/310,673, filed on Dec. 4, 2002, now abandoned, which claims thebenefit of U.S. provisional application Ser. No. 60/336,613, filed onDec. 4, 2001. U.S. application Ser. No. 10/948,737 is also acontinuation-in-part of and claims priority to U.S. application Ser. No.10/501,187, filed as a National stage of international application No.PCT/US03/00657, filed on Jan. 8, 2003, which claims the benefit of U.S.provisional application Ser. No. 60/345,637, filed on Jan. 8, 2002. U.S.application Ser. No. 10/948,737 is also a continuation-in-part of andclaims priority to U.S. application Ser. No. 10/081,124, filed on Feb.21, 2002, now abandoned, which claims the benefit of U.S. provisionalapplication Ser. No. 60/270,855, filed on Feb. 21, 2001. U.S.application Ser. No. 10/948,737 is also a continuation-in-part of andclaims priority to application PCT/US04/15421, filed on May 13, 2004,which claims the benefit of U.S. provisional application Ser. No.60/475,872, filed on Jun. 3, 2003. The contents of each of the precedingapplications is incorporated by reference in its entirety.

SEQUENCE LISTING AND TABLES

The content of the following submission on ASCII text file isincorporated herein by reference in its entirety: a computer readableform (CRF) of the Sequence Listing (file name: 636092106801SEQLIST.TXT,date created: Mar. 11, 2010, size: 8,697 kilobytes).

The present application also incorporates by reference Tables 7, 16, 17,33, 35, 36, and 37 filed concurrently herewith on ASCII text files,labeled Table 7.txt, Table 16.txt, Table 17.txt, Table 33.txt, Table35.txt, Table 36.txt, and Table 37.txt, respectively. The details ofthese Tables are further described later in this disclosure. These ASCIItext files were created on Feb. 23, 2010. The sizes of the Tables are asfollows: Table 7: 70 kilobytes; Table 16: 254 kilobytes; Table 17: 407kilobytes; Table 33: 603 kilobytes; Table 35: 379 kilobytes; Table 36:985 kilobytes; and Table 37: 518 kilobytes.

LENGTHY TABLES The patent contains a lengthy table section. A copy ofthe table is available in electronic form from the USPTO web site(http://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US08221983B2). Anelectronic copy of the table will also be available from the USPTO uponrequest and payment of the fee set forth in 37 CFR 1.19(b)(3).

FIELD OF THE INVENTION

The present invention relates to polynucleotides of human origin insubstantially isolated form and gene products that are differentiallyexpressed in cancer cells, and uses thereof.

BACKGROUND OF THE INVENTION

Cancer, like many diseases, is not the result of a single, well-definedcause, but rather can be viewed as several diseases, each caused bydifferent aberrations in informational pathways, that ultimately resultin apparently similar pathologic phenotypes. Identification ofpolynucleotides that correspond to genes that are differentiallyexpressed in cancerous, pre-cancerous, or low metastatic potential cellsrelative to normal cells of the same tissue type, provides the basis fordiagnostic tools, facilitates drug discovery by providing for targetsfor candidate agents, and further serves to identify therapeutic targetsfor cancer therapies that are more tailored for the type of cancer to betreated.

Identification of differentially expressed gene products also furthersthe understanding of the progression and nature of complex diseases suchas cancer, and is key to identifying the genetic factors that areresponsible for the phenotypes associated with development of, forexample, the metastatic phenotype. Identification of gene products thatare differentially expressed at various stages, and in various types ofcancers, can both provide for early diagnostic tests, and further serveas therapeutic targets. Additionally, the product of a differentiallyexpressed gene can be the basis for screening assays to identifychemotherapeutic agents that modulate its activity (e.g. its expression,biological activity, and the like).

Early disease diagnosis is of central importance to halting diseaseprogression, and reducing morbidity. Analysis of a patient's tumor toidentify the gene products that are differentially expressed, andadministration of therapeutic agent(s) designed to modulate the activityof those differentially expressed gene products, provides the basis formore specific, rational cancer therapy that may result in diminishedadverse side effects relative to conventional therapies. Furthermore,confirmation that a tumor poses less risk to the patient (e.g., that thetumor is benign) can avoid unnecessary therapies. In short,identification of genes and the encoded gene products that aredifferentially expressed in cancerous cells can provide the basis oftherapeutics, diagnostics, prognostics, therametrics, and the like.

For example, breast cancer is a leading cause of death among women. Oneof the priorities in breast cancer research is the discovery of newbiochemical markers that can be used for diagnosis, prognosis andmonitoring of breast cancer. The prognostic usefulness of these markersdepends on the ability of the marker to distinguish between patientswith breast cancer who require aggressive therapeutic treatment andpatients who should be monitored.

While the pathogenesis of breast cancer is unclear, transformation ofnon-tumorigenic breast epithelium to a malignant phenotype may be theresult of genetic factors, especially in women under 30 (Miki, et al.,Science, 266: 66-71, 1994). However, it is likely that other,non-genetic factors are also significant in the etiology of the disease.Regardless of its origin, breast cancer morbidity increasessignificantly if a lesion is not detected early in its progression.Thus, considerable effort has focused on the elucidation of earlycellular events surrounding transformation in breast tissue. Such efforthas led to the identification of several potential breast cancermarkers.

Thus, the identification of new markers associated with cancer, forexample, breast cancer, and the identification of genes involved intransforming cells into the cancerous phenotype, remains a significantgoal in the management of this disease. In exemplary aspects, theinvention described herein provides cancer diagnostics, prognostics,therametrics, and therapeutics based upon polynucleotides and/or theirencoded gene products.

SUMMARY OF THE INVENTION

The present invention provides methods and compositions useful indetection of cancerous cells, identification of agents that modulate thephenotype of cancerous cells, and identification of therapeutic targetsfor chemotherapy of cancerous cells. Cancerous prostate cells are ofparticular interest in each of these aspects of the invention. Morespecifically, the invention provides polynucleotides, as well aspolypeptides encoded thereby, that are differentially expressed inprostate cancer cells. Also provided are antibodies that specificallybind the encoded polypeptides. These polynucleotides, polypeptides andantibodies are thus useful in a variety of diagnostic, therapeutic, anddrug discovery methods. In some embodiments, a polynucleotide that isdifferentially expressed in prostate cancer cells can be used indiagnostic assays to detect prostate cancer cells. In other embodiments,a polynucleotide that is differentially expressed in prostate cancercells, and/or a polypeptide encoded thereby, is itself a target fortherapeutic intervention.

Accordingly, in one aspect the invention provides a method for detectinga cancerous prostate cell. In general, the method involves contacting atest sample obtained from a cell that is suspected of being a prostatecancer cell with a probe for detecting a gene product differentiallyexpressed in prostate cancer. Many embodiments of the invention involvea gene identifiable or comprising a sequence selected from the groupconsisting of SEQ ID NOS: 1-13996, contacting the probe and the geneproduct for a time sufficient for binding of the probe to the geneproduct; and comparing a level of binding of the probe to the samplewith a level of probe binding to a control sample obtained from acontrol prostate cell of known cancerous state. A modulated (i.e.increased or decreased) level of binding of the probe in the testprostate cell sample relative to the level of binding in a controlsample is indicative of the cancerous state of the test prostate cell.In certain embodiments, the level of binding of the probe in the testcell sample, usually in relation to at least one control gene, issimilar to binding of the probe to a cancerous cell sample. In certainother embodiments, the level of binding of the probe in the test cellsample, usually in relation to at least one control gene, is different,i.e. opposite, to binding of the probe to a non-cancerous cell sample.In specific embodiments, the probe is a polynucleotide probe and thegene product is nucleic acid. In other specific embodiments, the geneproduct is a polypeptide. In further embodiments, the gene product orthe probe is immobilized on an array.

In another aspect, the invention provides a method for assessing thecancerous phenotype (e.g., metastasis, metatstatic potential, aberrantcellular proliferation, and the like) of a prostate cell comprisingdetecting expression of a gene product in a test prostate cell sample,wherein the gene comprises a sequence selected from the group consistingof SEQ ID NOS: 1-13996; and comparing a level of expression of the geneproduct in the test prostate cell sample with a level of expression ofthe gene in a control cell sample. Comparison of the level of expressionof the gene in the test cell sample relative to the level of expressionin the control cell sample is indicative of the cancerous phenotype ofthe test cell sample. In specific embodiments, detection of geneexpression is by detecting a level of an RNA transcript in the test cellsample. In other specific embodiments detection of expression of thegene is by detecting a level of a polypeptide in a test sample.

In another aspect, the invention provides a method for suppressing orinhibiting a cancerous phenotype of a cancerous cell, the methodcomprising introducing into a mammalian cell an expression modulatoryagent (e.g. an antisense molecule, small molecule, antibody,neutralizing antibody, inhibitory RNA molecule, etc.) to inhibition ofexpression of a gene identified by a sequence selected from the groupconsisting of SEQ ID NOS: 1-13996. Inhibition of expression of the geneinhibits development of a cancerous phenotype in the cell. In specificembodiments, the cancerous phenotype is metastasis, aberrant cellularproliferation relative to a normal cell, or loss of contact inhibitionof cell growth. In the context of this invention “expression” of a geneis intended to encompass the expression of an activity of a geneproduct, and, as such, inhibiting expression of a gene includesinhibiting the activity of a product of the gene.

In another aspect, the invention provides a method for assessing thetumor burden of a subject, the method comprising detecting a level of adifferentially expressed gene product in a test sample from a subjectsuspected of or having a tumor, the differentially expressed geneproduct comprising a sequence selected from the group consisting of SEQID NOS: 1-13996. Detection of the level of the gene product in the testsample is indicative of the tumor burden in the subject.

In another aspect, the invention provides a method for identifying agene product as a target for a cancer therapeutic, the method comprisingcontacting a cancerous cell expressing a candidate gene product with ananti-cancer agent, wherein the candidate gene product corresponds to asequence selected from the group consisting of SEQ ID NOS: 1-13996; andanalyzing the effect of the anti-cancer agent upon a biological activityof the candidate gene product and/or upon a cancerous phenotype of thecancerous cell. Modulation of the biological activity of the candidategene product and modulation of the cancerous phenotype of the cancerouscell indicates the candidate gene product is a target for a cancertherapeutic. In specific embodiments, the cancerous cell is a cancerousprostate cell. In other specific embodiments, the inhibitor is anantisense oligonucleotide. In further embodiments, the cancerousphenotype is aberrant cellular proliferation relative to a normal cell,or colony formation due to loss of contact inhibition of cell growth.

In another aspect, the invention provides a method for identifyingagents that modulate (i.e. increase or decrease) the biological activityof a gene product differentially expressed in a cancerous cell, themethod comprising contacting a candidate agent with a differentiallyexpressed gene product, the differentially expressed gene productcorresponding to a sequence selected from the group consisting of SEQ IDNOS: 1-13996; and detecting a modulation in a biological activity of thegene product relative to a level of biological activity of the geneproduct in the absence of the candidate agent. In specific embodiments,the detecting is by identifying an increase or decrease in expression ofthe differentially expressed gene product. In other specificembodiments, the gene product is mRNA or cDNA prepared from the mRNAgene product. In further embodiments, the gene product is a polypeptide.

In another aspect, the invention provides a method of inhibiting growthof a tumor cell by modulating expression of a gene product, where thegene product is encoded by a gene identified by a sequence selected fromthe group consisting of: SEQ ID NOS:1-13996.

The invention provides a method of determining the cancerous state of acell, comprising detecting a level of a product of a gene in a test cellwherein said gene is defined by a sequence selected from a groupconsisting of SEQ ID NOS:1-13996 wherein the cancerous state of the testcell is indicated by detection of said level and comparison to a controllevel of said gene product. In certain embodiments of this method, thegene product is a nucleic acid or a polypeptide. In certain embodimentsof this method, the gene product is immobilized on an array. In oneembodiment of this method, the control level is a level of said geneproduct associated with a control cell of known cancerous state. Inother embodiments of this method, the known cancerous state is anon-cancerous state. In another embodiment of this method, the leveldiffers from the control level by at least two fold, indicating the testcell is not of the same cancerous state as that indicated by the controllevel.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a schematic showing the alignment of the sequences(represented by single lines) that resulted in the assembly of thecontig (represented by the bars in the lower portion of the figure).

FIGS. 2-17 are graphs showing the expression profiles of the genes ofGroup 1.

FIGS. 18-21 are graphs showing the expression profiles of the genes ofGroup 2. In addition to the figures described above, the applicationalso includes Tables 11-13A-B, as well as a Sequence Listing.

FIG. 22 is a table showing the expression of condroitin 4-Osulfotransferase 2 (C4S-2) in cancer versus normal cells, as determinedby microarray analysis.

FIG. 23 is a bar graph showing C4S-2 mRNA expression in laser capturemicrodissected tissues, as determined by quantitative PCR analysis.

FIG. 24 is a bar graph showing C4S-2 mRNA expression in tissue samples.

FIG. 25 is a bar graph showing C4S-2 mRNA expression in prostate celllines.

FIG. 26 is a table of antisense polynucleotides, directed against C4S-2.

FIG. 27 is a table of inhibitory RNA polynucleotides, directed againstC4S-2.

FIG. 28 is two line graphs showing the effect of C4S-2 antisensemolecules on growth of PC3 cells.

FIG. 29 is a line graph showing the effect of C4S-2 antisense moleculeson growth of MDA PCa 2b cells.

FIG. 30 is a bar graph showing the effects of C4S-2 antisense moleculeson PC3 growth in soft-agar.

FIG. 31 is two line graphs showing the effects of C4S-2 antisensemolecules on growth of MDA PCa 2b cells growth in soft-agar.

FIGS. 32A-D show the effects of C4S-2 antisense molecules on MDA PCa 2bspheroids. FIGS. 32A-C are photographs of spheroids. FIG. 32D is a bargraph showing LDH ratios.

FIG. 33A-C show the effects of C4S-2 antisense molecules on MRC9 cells.

FIG. 33A is a graph of cytotoxicity. FIG. 33B is a graph showingrelative mRNA expression of C4S-2 in cell lines. FIG. 33C is a panel ofphotographs of MRC9 cells.

FIG. 34 is a three dimensional bar graph showing effects of C4S-2antisense molecules on 184B5 cell cytotoxicity.

FIG. 35 is a composite of graphs showing effects of C4S-2 antisensemolecules on 184B5 and MRC9 cell proliferation.

FIG. 36 is a table of genes that are co-regulated with C4S-2.

FIG. 37 is a sequence alignment of mouse C4S-2 (top) and human C4S-2(bottom).

FIG. 38 is three panels of autoradiographs showing expression of GAKpolypeptide in different cell lines.

FIG. 39 is a graph of a hydropathy plot and a table showing thehydrophobic regions of DKFZp566I133.

FIG. 40 is six panels of photographs of MDA-231 cells exposed to C180-7,C180-8 and positive control antisense (AS) and control (RC)oligonucleotides.

FIG. 41 is an alignment of spot ID 22793 and spot ID 26883.

FIG. 42 is a figure of three sequence alignments showing the mapping ofeach of three sequences onto VMP1 (DKFZ).

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides polynucleotides, as well as polypeptidesencoded thereby, that are differentially expressed in cancer cells.Methods are provided in which these polynucleotides and polypeptides areused for detecting and reducing the growth of cancer cells. Alsoprovided are methods in which the polynucleotides and polypeptides ofthe invention are used in a variety of diagnostic and therapeuticapplications for cancer. The invention finds use in the prevention,treatment, detection or research into any cancer, including prostrate,pancreas, colon, brain, lung, breast, bone, skin cancers. For example,the invention finds use in the prevention, treatment, detection of orresearch into endocrine system cancers, such as cancers of the thyroid,pituitary, and adrenal glands and the pancreatic islets;gastrointestinal cancers, such as cancer of the anus, colon, esophagus,gallbladder, stomach, liver, and rectum; genitourinary cancers such ascancer of the penis, prostate and testes; gynecological cancers, such ascancer of the ovaries, cervix, endometrium, uterus, fallopian tubes,vagina, and vulva; head and neck cancers, such as hypopharyngeal,laryngeal, oropharyngeal cancers, lip, mouth and oral cancers, cancer ofthe salivary gland, cancer of the digestive tract and sinus cancer;leukemia; lymphomas including Hodgkin's and non-Hodgkin's lymphoma;metastatic cancer; myelomas; sarcomas; skin cancer; urinary tractcancers including bladder, kidney and urethral cancers; and pediatriccancers, such as pediatric brain tumors, leukemia, lymphomas, sarcomas,liver cancer and neuroblastorna and retinoblastoma.

Before the present invention is described, it is to be understood thatthis invention is not limited to particular embodiments described, assuch may, of course, vary. It is also to be understood that theterminology used herein is for the purpose of describing particularembodiments only, and is not intended to be limiting.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although any methods andmaterials similar or equivalent to those described herein can be used inthe practice or testing of the present invention, the preferred methodsand materials are now described. All publications and patentapplications mentioned herein are incorporated herein by reference todisclose and describe the methods and/or materials in connection withwhich the publications are cited.

It must be noted that as used herein and in the appended claims, thesingular forms “a”, “and”, and “the” include plural referents unless thecontext clearly dictates otherwise. Thus, for example, reference to “apolynucleotide” includes a plurality of such polynucleotides andreference to “the cancer cell” includes reference to one or more cellsand equivalents thereof known to those skilled in the art, and so forth.

The publications and applications discussed herein are provided solelyfor their disclosure prior to the filing date of the presentapplication. Nothing herein is to be construed as an admission that thepresent invention is not entitled to antedate such publication by virtueof prior invention. Further, the dates of publication provided may bedifferent from the actual publication dates which may need to beindependently confirmed.

DEFINITIONS

The terms “polynucleotide” and “nucleic acid”, used interchangeablyherein, refer to polymeric forms of nucleotides of any length, eitherribonucleotides or deoxynucleotides. Thus, these terms include, but arenot limited to, single-, double-, or multi-stranded DNA or RNA, genomicDNA, cDNA, DNA-RNA hybrids, or a polymer comprising purine andpyrimidine bases or other natural, chemically or biochemically modified,non-natural, or derivatized nucleotide bases. These terms furtherinclude, but are not limited to, mRNA or cDNA that comprise intronicsequences (see, e.g., Niwa et al. (1999) Cell 99(7):691-702). Thebackbone of the polynucleotide can comprise sugars and phosphate groups(as may typically be found in RNA or DNA), or modified or substitutedsugar or phosphate groups. Alternatively, the backbone of thepolynucleotide can comprise a polymer of synthetic subunits such asphosphoramidites and thus can be an oligodeoxynucleotide phosphoramidateor a mixed phosphoramidate-phosphodiester oligomer. Peyrottes et al.(1996) Nucl. Acids Res. 24:1841-1848; Chaturvedi et al. (1996) Nucl.Acids Res. 24:2318-2323. A polynucleotide may comprise modifiednucleotides, such as methylated nucleotides and nucleotide analogs,uracyl, other sugars, and linking groups such as fluororibose andthioate, and nucleotide branches. The sequence of nucleotides may beinterrupted by non-nucleotide components. A polynucleotide may befurther modified after polymerization, such as by conjugation with alabeling component. Other types of modifications included in thisdefinition are caps, substitution of one or more of the naturallyoccurring nucleotides with an analog, and introduction of means forattaching the polynucleotide to proteins, metal ions, labelingcomponents, other polynucleotides, or a solid support. The term“polynucleotide” also encompasses peptidic nucleic acids (Pooga et alCurr Cancer Drug Targets. (2001) 1:231-9).

A “gene product” is a biopolymeric product that is expressed or producedby a gene. A gene product may be, for example, an unspliced RNA, anmRNA, a splice variant mRNA, a polypeptide, a post-translationallymodified polypeptide, a splice variant polypeptide etc. Also encompassedby this term is biopolymeric products that are made using an RNA geneproduct as a template (i.e. cDNA of the RNA). A gene product may be madeenzymatically, recombinantly, chemically, or within a cell to which thegene is native. In many embodiments, if the gene product isproteinaceous, it exhibits a biological activity. In many embodiments,if the gene product is a nucleic acid, it can be translated into aproteinaceous gene product that exhibits a biological activity.

A composition (e.g. a polynucleotide, polypeptide, antibody, or hostcell) that is “isolated” or “in substantially isolated form” refers to acomposition that is in an environment different from that in which thecomposition naturally occurs. For example, a polynucleotide that is insubstantially isolated form is outside of the host cell in which thepolynucleotide naturally occurs, and could be a purified fragment ofDNA, could be part of a heterologous vector, or could be containedwithin a host cell that is not a host cell from which the polynucleotidenaturally occurs. The term “isolated” does not refer to a genomic orcDNA library, whole cell total protein or mRNA preparation, genomic DNApreparation, or an isolated human chromosome. A composition which is insubstantially isolated form is usually substantially purified.

As used herein, the term “substantially purified” refers to a compound(e.g., a polynucleotide, a polypeptide or an antibody, etc.) that isremoved from its natural environment and is usually at least 60% free,preferably 75% free, and most preferably 90% free from other componentswith which it is naturally associated. Thus, for example, a compositioncontaining A is “substantially free of” B when at least 85% by weight ofthe total A+B in the composition is A. Preferably, A comprises at leastabout 90% by weight of the total of A+B in the composition, morepreferably at least about 95% or even 99% by weight. In the case ofpolynucleotides, “A” and “B” may be two different genes positioned ondifferent chromosomes or adjacently on the same chromosome, or twoisolated cDNA species, for example.

The terms “polypeptide” and “protein”, interchangeably used herein,refer to a polymeric form of amino acids of any length, which caninclude coded and non-coded amino acids, chemically or biochemicallymodified or derivatized amino acids, and polypeptides having modifiedpeptide backbones. The term includes fusion proteins, including, but notlimited to, fusion proteins with a heterologous amino acid sequence,fusions with heterologous and homologous leader sequences, with orwithout N-terminal methionine residues; immunologically tagged proteins;and the like.

“Heterologous” refers to materials that are derived from differentsources (e.g., from different genes, different species, etc.).

As used herein, the terms “a gene that is differentially expressed in acancer cell,” and “a polynucleotide that is differentially expressed ina cancer cell” are used interchangeably herein, and generally refer to apolynucleotide that represents or corresponds to a gene that isdifferentially expressed in a cancerous cell when compared with a cellof the same cell type that is not cancerous, e.g., mRNA is found atlevels at least about 25%, at least about 50% to about 75%, at leastabout 90%, at least about 1.5-fold, at least about 2-fold, at leastabout 5-fold, at least about 10-fold, or at least about 50-fold or more,different (e.g., higher or lower). The comparison can be made in tissue,for example, if one is using in situ hybridization or another assaymethod that allows some degree of discrimination among cell types in thetissue. The comparison may also or alternatively be made between cellsremoved from their tissue source.

“Differentially expressed polynucleotide” as used herein refers to anucleic acid molecule (RNA or DNA) comprising a sequence that representsa differentially expressed gene, e.g., the differentially expressedpolynucleotide comprises a sequence (e.g., an open reading frameencoding a gene product; a non-coding sequence) that uniquely identifiesa differentially expressed gene so that detection of the differentiallyexpressed polynucleotide in a sample is correlated with the presence ofa differentially expressed gene in a sample. “Differentially expressedpolynucleotides” is also meant to encompass fragments of the disclosedpolynucleotides, e.g., fragments retaining biological activity, as wellas nucleic acids homologous, substantially similar, or substantiallyidentical (e.g., having about 90% sequence identity) to the disclosedpolynucleotides.

“Corresponds to” or “represents” when used in the context of, forexample, a polynucleotide or sequence that “corresponds to” or“represents” a gene means that at least a portion of a sequence of thepolynucleotide is present in the gene or in the nucleic acid geneproduct (e.g., mRNA or cDNA). A subject nucleic acid may also be“identified” by a polynucleotide if the polynucleotide corresponds to orrepresents the gene. Genes identified by a polynucleotide may have allor a portion of the identifying sequence wholly present within an exonof a genomic sequence of the gene, or different portions of the sequenceof the polynucleotide may be present in different exons (e.g., such thatthe contiguous polynucleotide sequence is present in an mRNA, eitherpre- or post-splicing, that is an expression product of the gene). Insome embodiments, the polynucleotide may represent or correspond to agene that is modified in a cancerous cell relative to a normal cell. Thegene in the cancerous cell may contain a deletion, insertion,substitution, or translocation relative to the polynucleotide and mayhave altered regulatory sequences, or may encode a splice variant geneproduct, for example. The gene in the cancerous cell may be modified byinsertion of an endogenous retrovirus, a transposable element, or othernaturally occurring or non-naturally occurring nucleic acid. In mostcases, a polynucleotide corresponds to or represents a gene if thesequence of the polynucleotide is most identical to the sequence of agene or its product (e.g. mRNA or cDNA) as compared to other genes ortheir products. In most embodiments, the most identical gene isdetermined using a sequence comparison of a polynucleotide to a databaseof polynucleotides (e.g. GenBank) using the BLAST program at defaultsettings For example, if the most similar gene in the human genome to anexemplary polynucleotide is the protein kinase C gene, the exemplarypolynucleotide corresponds to protein kinase C. In most cases, thesequence of a fragment of an exemplary polynucleotide is at least 95%,96%, 97%, 98%, 99% or up to 100% identical to a sequence of at least 15,20, 25, 30, 35, 40, 45, or 50 contiguous nucleotides of a correspondinggene or its product (mRNA or cDNA), when nucleotides that are “N”represent G, A, T or C.

An “identifying sequence” is a minimal fragment of a sequence ofcontiguous nucleotides that uniquely identifies or defines apolynucleotide sequence or its complement. In many embodiments, afragment of a polynucleotide uniquely identifies or defines apolynucleotide sequence or its complement. In some embodiments, theentire contiguous sequence of a gene, cDNA, EST, or other providedsequence is an identifying sequence.

“Diagnosis” as used herein generally includes determination of asubject's susceptibility to a disease or disorder, determination as towhether a subject is presently affected by a disease or disorder,prognosis of a subject affected by a disease or disorder (e.g.,identification of pre-metastatic or metastatic cancerous states, stagesof cancer, or responsiveness of cancer to therapy), and use oftherametrics (e.g., monitoring a subject's condition to provideinformation as to the effect or efficacy of therapy).

As used herein, the term “a polypeptide associated with cancer” refersto a polypeptide encoded by a polynucleotide that is differentiallyexpressed in a cancer cell.

The term “biological sample” encompasses a variety of sample typesobtained from an organism and can be used in a diagnostic or monitoringassay. The term encompasses blood and other liquid samples of biologicalorigin, solid tissue samples, such as a biopsy specimen or tissuecultures or cells derived therefrom and the progeny thereof. The termencompasses samples that have been manipulated in any way after theirprocurement, such as by treatment with reagents, solubilization, orenrichment for certain components. The term encompasses a clinicalsample, and also includes cells in cell culture, cell supernatants, celllysates, serum, plasma, biological fluids, and tissue samples.

The terms “treatment”, “treating”, “treat” and the like are used hereinto generally refer to obtaining a desired pharmacologic and/orphysiologic effect. The effect may be prophylactic in terms ofcompletely or partially preventing a disease or symptom thereof and/ormay be therapeutic in terms of a partial or complete stabilization orcure for a disease and/or adverse effect attributable to the disease.“Treatment” as used herein covers any treatment of a disease in amammal, particularly a human, and includes: (a) preventing the diseaseor symptom from occurring in a subject which may be predisposed to thedisease or symptom but has not yet been diagnosed as having it; (b)inhibiting the disease symptom, i.e., arresting its development; or (c)relieving the disease symptom, i.e., causing regression of the diseaseor symptom.

The terms “individual,” “subject,” “host,” and “patient,” usedinterchangeably herein and refer to any mammalian subject for whomdiagnosis, treatment, or therapy is desired, particularly humans. Othersubjects may include cattle, dogs, cats, guinea pigs, rabbits, rats,mice, horses, and the like.

A “host cell”, as used herein, refers to a microorganism or a eukaryoticcell or cell line cultured as a unicellular entity which can be, or hasbeen, used as a recipient for a recombinant vector or other transferpolynucleotides, and include the progeny of the original cell which hasbeen transfected. It is understood that the progeny of a single cell maynot necessarily be completely identical in morphology or in genomic ortotal DNA complement as the original parent, due to natural, accidental,or deliberate mutation.

The terms “cancer”, “neoplasm”, “tumor”, and “carcinoma”, are usedinterchangeably herein to refer to cells which exhibit relativelyautonomous growth, so that they exhibit an aberrant growth phenotypecharacterized by a significant loss of control of cell proliferation. Ingeneral, cells of interest for detection or treatment in the presentapplication include precancerous (e.g., benign), malignant,pre-metastatic, metastatic, and non-metastatic cells. Detection ofcancerous cells is of particular interest.

The term “normal” as used in the context of “normal cell,” is meant torefer to a cell of an untransformed phenotype or exhibiting a morphologyof a non-transformed cell of the tissue type being examined.

“Cancerous phenotype” generally refers to any of a variety of biologicalphenomena that are characteristic of a cancerous cell, which phenomenacan vary with the type of cancer. The cancerous phenotype is generallyidentified by abnormalities in, for example, cell growth orproliferation (e.g., uncontrolled growth or proliferation), regulationof the cell cycle, cell mobility, cell-cell interaction, or metastasis,etc.

“Therapeutic target” generally refers to a gene or gene product that,upon modulation of its activity (e.g., by modulation of expression,biological activity, and the like), can provide for modulation of thecancerous phenotype.

As used throughout, “modulation” is meant to refer to an increase or adecrease in the indicated phenomenon (e.g., modulation of a biologicalactivity refers to an increase in a biological activity or a decrease ina biological activity).

As used herein a “Group I type tumor” is a tumor comprising cells that,relative to a non-cancer cell of the same tissue type, exhibit increasedexpression of a gene product encoded by at least one or more of thefollowing genes: IGF2, TTK, MAPKAPK2, MARCKS, BBS2, CETN2 CGI-148protein, FGFR4, FHL3, FLJ22066, KIP2, MGC:29604, NQO2, and OGG1.

As used herein a “Group II type tumor” is a tumor comprising cells that,relative to a non-cancer cell of the same tissue type, exhibit increasedexpression of a gene product encoded by at least one or more of thefollowing genes: IFITM (1-8U; 1-8D; 9-27), ITAK, and BIRC3/H-IAP1.

As used herein a “Group I+II type tumor” is a tumor comprising cellsthat, relative to a non-cancer cell of the same tissue type, exhibitincreased expression of 1) a gene product encoded by at least one ormore of the following genes: IGF2, TTK, MAPKAPK2, MARCKS, BBS2, CETN2CGI-148 protein, FGFR4, FHL3, FLJ22066, KIP2, MGC:29604, NQO2, and OGG1;and a gene product encoded by at least one or more of the followinggenes 2) IFITM (1-8U; 1-8D; 9-27), ITAK, and BIRC3/H-IAP1.

By “chondroitin 4-O sulfotransferase” is meant any polypeptidecomposition that exhibits chondroitin 4-O sulfotransferase activity.Examples of chondroitin 4-O sulfotransferases include chondroitin 4-Osulfotransferase-1, -2, -3, defined by NCBI accession numbers AAF81691,AAF81692, and AAM55481, respectively. Assays for determining whether apolypeptide has chondroitin 4-O sulfotransferase activity are describedin Burkart & Wong (Anal Biochem 274:131-137 (1999)), and furtherdescribed below. Variants of chondroitin 4-O sulfotransferase includeenzymes that retain chondroitin 4-O sulfotransferase activity, i.e. asulfotransferase activity that is specific for chondroitin over othersubstrates. Variants of chondroitin 4-O sulfotransferase-1, -2, -3 thatretain biological activity may be produced by substituting amino acidsthat are in equivalent positions between two chondroitin 4-Osulfotransferases, such as chondroitin 4-O sulfotransferase-1 andchondroitin 4-O sulfotransferase-2. A chondroitin 4-O sulfotransferaseactivity of interest is chondroitin 4-O sulfotransferase 2, (C4S-2).

By “chondroitin 4-O sulfotransferase 2” is meant a polypeptide that haschondroitin 4-O sulfotransferase activity and has significant sequenceidentity to the chondroitin 4-O sulfotransferase 2 of humans (NCBIaccession number NP_(—)061111) or mouse (NCBI accession numberNP_(—)067503). The alignment between these two polypeptides (mouse C4S-2at the top and human C4S-2 at the bottom) is shown in FIG. 37 (fromHiraoaka at al JBC 2000 275: 20188-96). Conserved sequences that areactive sites, important for binding phosphate and phosphosulphategroups, are underlined in this figure. Variants of chondroitin 4-Osulfotransferase 2 that have chondroitin 4-O sulfotransferase 2 activityinclude the human and mice chondroitin 4-O sulfotransferase 2polypeptides, and, for example, polypeptides that contain substitutionsof amino acids at equivalent positions from e.g. the mouse to the humanpolypeptidies. Amino acids at positions 4, 16, 17, 28 and 29 areexamples of such amino acids. Chondroitin 4-O sulfotransferase 2 hasspecificity for certain substrates with respect to other chondroitin 4-Osulfotransferases.

With regard to chondroitin 4-O sulfotransferases, further references ofinterest include Hiraoaka at al JBC 2000 275: 20188-96, Ricciardelli etal. Cancer Res. 1999 May 15; 59(10):2324-8, Ricciardelli et al. ClinCancer Res. 1997 June; 3(6):983-92, Lida et al. Semin Cancer Biol. 1996June; 7(3):155-62, Yamori et al. J Cell Biochem. 1988 April;36(4):405-16, Denholm et al. Eur J. Pharmacol. 2001 Mar. 30;416(3):213-21 and Bowman and Bertozzi Chem. Biol. 1999 January;6(1):R9-R22.

A “chondroitin 4-O sulfotransferase-related disorder” is a disorder thatis associated with the abnormal expression (i.e. increased or decreasedexpression) of a chondroitin 4-O sulfotransferase or variant thereof. Incertain embodiments, the “chondroitin 4-O sulfotransferase-relateddisorder” is a “chondroitin 4-O sulfotransferase-2-related disorder”associated with the abnormal expression of chondroitin 4-Osulfotransferase-2 or a variant thereof. These disorders are usuallyrelated to cancer, in particular cancers of the breast, colon, lung,brain, skin etc. In certain embodiments, the disorder relates toprostate cancer.

By “cyclin G associated kinase”, or “GAK” is meant any polypeptidecomposition that exhibits cyclin G associated kinase activity. Examplesof cyclin G associated kinase include the polypeptide defined by NCBIaccession number XM_(—)003450, NM_(—)005255, NP_(—)005246 andNM_(—)031030. Assays for determining whether a polypeptide has cyclin Gassociated kinase activity are described in Ausubel et al., eds., 1998,Current Protocols in Molecular Biology, John Wiley & Sons, NY. Variantsof the human cyclin G associated kinase that retain biological activitymay be produced by, inter alia, substituting amino acids that are inequivalent positions between two cyclin G associated kinases, such asthe cyclin G associated kinases from rat and humans.

With regard to cyclin G associated kinases, further references ofinterest include: Kanaoka et al, FEBS Lett. 1997 Jan. 27; 402(1):73-80;Kimura et al, Genomics. 1997 Sep. 1; 44(2):179-87; Greener et al, JBiol. Chem. 2000 Jan. 14; 275(2):1365-70; and Korolchuk et al, Traffic.2002 June; 3(6):428-39.

“DKFZP566I133” and “DKFZ” are used interchangeably herein to refer to apolypeptide composition that exhibits DKFZP566I133 activity. Assays fordetermining whether a polypeptide has DKFZP566I133 activity (i.e. fordetermining whether DKFZP566I133 may have intracytoplasmatic vacuolepromoting activity) are described in Dusetti et al, (Biochem Biophys ResCommun. 2002 Jan. 18; 290(2):641-9). Variants of the DKFZP566I133 thatretain biological activity may be produced by, inter alia, substitutingamino acids that are in equivalent positions between two DKFZP566I133,such as the DKFZp566I133 from rat and humans. DKFZ is also known asVMP1, or vacuole membrane protein 1.

Alternatively, “DKFZP566I133”, or “DKFZ” refers to an amino acidsequence defined by NCBI accession number NP_(—)112200, AAH09758,NM_(—)138839, and NM_(—)030938, polynucleotides encoding the amino acidsequences set forth in these accession numbers (SEQ ID NO:3017 and SEQID NO: 3018, respectively).

In addition, “DKFZP566I133”, or “DKFZ” refers to the polynucleotidesequences represented by Spot ID NOS 22793, 26883 and 27450 (SEQ ID NOS:2779-2780 and SEQ ID NOS: 2781-2782 and SEQ ID NOS:2964-2965,respectively). FIG. 41 shows an alignment between Spot ID NOS: 22793,26883 and VMP1 (NM_(—)030938) (i.e. DKFZ), identifying a VMP1 or DKFZgene product as corresponding to these spot IDs. FIG. 42 depictsfragments of Spot ID NOS 22793, 26883, 27450 which align with VMP1 (SEQID NOS 3019, 3020, and 3021 respectively). These fragments, or theirencoded products, may also be used as a DKFZ identifying sequence.

Polynucleotide Compositions

The present invention provides isolated polynucleotides that containnucleic acids that are differentially expressed in cancer cells. Thepolynucleotides, as well as any polypeptides encoded thereby, find usein a variety of therapeutic and diagnostic methods.

The scope of the invention with respect to compositions containing theisolated polynucleotides useful in the methods described hereinincludes, but is not necessarily limited to, polynucleotides having(i.e., comprising) a sequence set forth in any one of the polynucleotidesequences provided herein, or fragment thereof; polynucleotides obtainedfrom the biological materials described herein or other biologicalsources (particularly human sources) by hybridization under stringentconditions (particularly conditions of high stringency); genescorresponding to the provided polynucleotides; cDNAs corresponding tothe provided polynucleotides; variants of the provided polynucleotidesand their corresponding genes, particularly those variants that retain abiological activity of the encoded gene product (e.g., a biologicalactivity ascribed to a gene product corresponding to the providedpolynucleotides as a result of the assignment of the gene product to aprotein family(ies) and/or identification of a functional domain presentin the gene product). Other nucleic acid compositions contemplated byand within the scope of the present invention will be readily apparentto one of ordinary skill in the art when provided with the disclosurehere. “Polynucleotide” and “nucleic acid” as used herein with referenceto nucleic acids of the composition is not intended to be limiting as tothe length or structure of the nucleic acid unless specificallyindicated.

The invention features polynucleotides that represent genes that areexpressed in human tissue, specifically polynucleotides that aredifferentially expressed in tissues containing cancerous cells. Nucleicacid compositions described herein of particular interest are at leastabout 15 by in length, at least about 30 by in length, at least about 50by in length, at least about 100 bp, at least about 200 by in length, atleast about 300 by in length, at least about 500 by in length, at leastabout 800 by in length, at least about 1 kb in length, at least about2.0 kb in length, at least about 3.0 kb in length, at least about 5 kbin length, at least about 10 kb in length, at least about 50 kb inlength and are usually less than about 200 kb in length. Thesepolynucleotides (or polynucleotide fragments) have uses that include,but are not limited to, diagnostic probes and primers as startingmaterials for probes and primers, as discussed herein.

The subject polynucleotides usually comprise a sequence set forth in anyone of the polynucleotide sequences provided herein, for example, in thesequence listing, incorporated by reference in a table (e.g. by an NCBIaccession number), a cDNA deposited at the A.T.C.C., or a fragment orvariant thereof. A “fragment” or “portion” of a polynucleotide is acontiguous sequence of residues at least about 10 nt to about 12 nt, 15nt, 16 nt, 18 nt or 20 nt in length, usually at least about 22 nt, 24nt, 25 nt, 30 nt, 40 nt, 50 nt, 60 nt, 70 nt, 80 nt, 90 nt, 100 nt to atleast about 150 nt, 200 nt, 250 nt, 300 nt, 350 nt, 400 nt, 500 nt, 800nt or up to about 1000 nt, 1500 or 2000 nt in length. In someembodiments, a fragment of a polynucleotide is the coding sequence of apolynucleotide. A fragment of a polynucleotide may start at position 1(i.e. the first nucleotide) of a nucleotide sequence provided herein, ormay start at about position 10, 20, 30, 50, 75, 100, 150, 200, 250, 300,350, 400, 450, 500, 600, 700, 800, 900, 1000, 1500 or 2000, or an ATGtranslational initiation codon of a nucleotide sequence provided herein.In this context “about” includes the particularly recited value or avalue larger or smaller by several (5, 4, 3, 2, or 1) nucleotides. Thedescribed polynucleotides and fragments thereof find use ashybridization probes, PCR primers, BLAST probes, or as an identifyingsequence, for example.

The subject nucleic acids may be variants or degenerate variants of asequence provided herein. In general, a variants of a polynucleotideprovided herein have a fragment of sequence identity that is greaterthan at least about 65%, greater than at least about 70%, greater thanat least about 75%, greater than at least about 80%, greater than atleast about 85%, or greater than at least about 90%, 95%, 96%, 97%, 98%,99% or more (i.e. 100%) as compared to an identically sized fragment ofa provided sequence as determined by the Smith-Waterman homology searchalgorithm as implemented in MPSRCH program (Oxford Molecular). For thepurposes of this invention, a preferred method of calculating percentidentity is the Smith-Waterman algorithm. Global DNA sequence identityshould be greater than 65% as determined by the Smith-Waterman homologysearch algorithm as implemented in MPSRCH program (Oxford Molecular)using an gap search with the following search parameters: gap openpenalty, 12; and gap extension penalty, 1.

The subject nucleic acid compositions include full-length cDNAs or mRNAsthat encompass an identifying sequence of contiguous nucleotides fromany one of the polynucleotide sequences provided herein.

As discussed above, the polynucleotides useful in the methods describedherein also include polynucleotide variants having sequence similarityor sequence identity. Nucleic acids having sequence similarity aredetected by hybridization under low stringency conditions, for example,at 50° C. and 10×SSC (0.9 M saline/0.09 M sodium citrate) and remainbound when subjected to washing at 55° C. in 1×SSC. Sequence identitycan be determined by hybridization under high stringency conditions, forexample, at 50° C. or higher and 0.1×SSC (9 mM saline/0.9 mM sodiumcitrate). Hybridization methods and conditions are well known in theart, see, e.g., U.S. Pat. No. 5,707,829. Nucleic acids that aresubstantially identical to the provided polynucleotide sequences, e.g.allelic variants, genetically altered versions of the gene, etc., bindto the provided polynucleotide sequences under stringent hybridizationconditions. By using probes, particularly labeled probes of DNAsequences, one can isolate homologous or related genes. The source ofhomologous genes can be any species, e.g. primate species, particularlyhuman; rodents, such as rats and mice; canines, felines, bovines,ovines, equines, yeast, nematodes, etc.

In one embodiment, hybridization is performed using a fragment of atleast 15 contiguous nucleotides (nt) of at least one of thepolynucleotide sequences provided herein. That is, when at least 15contiguous nt of one of the disclosed polynucleotide sequences is usedas a probe, the probe will preferentially hybridize with a nucleic acidcomprising the complementary sequence, allowing the identification andretrieval of the nucleic acids that uniquely hybridize to the selectedprobe. Probes from more than one polynucleotide sequence provided hereincan hybridize with the same nucleic acid if the cDNA from which theywere derived corresponds to one mRNA.

Polynucleotides contemplated for use in the invention also include thosehaving a sequence of naturally occurring variants of the nucleotidesequences (e.g., degenerate variants (e.g., sequences that encode thesame polypeptides but, due to the degenerate nature of the genetic code,different in nucleotide sequence), allelic variants, etc.). Variants ofthe polynucleotides contemplated by the invention are identified byhybridization of putative variants with nucleotide sequences disclosedherein, preferably by hybridization under stringent conditions. Forexample, by using appropriate wash conditions, variants of thepolynucleotides described herein can be identified where the allelicvariant exhibits at most about 25-30% base pair (bp) mismatches relativeto the selected polynucleotide probe. In general, allelic variantscontain 15-25% by mismatches, and can contain as little as even 5-15%,or 2-5%, or 1-2% by mismatches, as well as a single by mismatch.

The invention also encompasses homologs corresponding to any one of thepolynucleotide sequences provided herein, where the source of homologousgenes can be any mammalian species, e.g., primate species, particularlyhuman; rodents, such as rats; canines, felines, bovines, ovines,equines, yeast, nematodes, etc. Between mammalian species, e.g., humanand mouse, homologs generally have substantial sequence similarity,e.g., at least 75% sequence identity, usually at least 80%%, at least85, at least 90%, at least 95%, at least 96%, at least 97%, at least98%, at least 99% or even 100% identity between nucleotide sequences.Sequence similarity is calculated based on a reference sequence, whichmay be a subset of a larger sequence, such as a conserved motif, codingregion, flanking region, etc. A reference sequence will usually be atleast about a fragment of a polynucleotide sequence and may extend tothe complete sequence that is being compared. Algorithms for sequenceanalysis are known in the art, such as gapped BLAST, described inAltschul, et al. Nucleic Acids Res. (1997) 25:3389-3402, or TeraBLASTavailable from TimeLogic Corp. (Crystal Bay, Nev.).

The subject nucleic acids can be cDNAs or genomic DNAs, as well asfragments thereof, particularly fragments that encode a biologicallyactive gene product and/or are useful in the methods disclosed herein(e.g., in diagnosis, as a unique identifier of a differentiallyexpressed gene of interest, etc.). The term “cDNA” as used herein isintended to include all nucleic acids that share the arrangement ofsequence elements found in native mature mRNA species, where sequenceelements are exons and 3′ and 5′ non-coding regions. Normally mRNAspecies have contiguous exons, with the intervening introns, whenpresent, being removed by nuclear RNA splicing, to create a continuousopen reading frame encoding a polypeptide. mRNA species can also existwith both exons and introns, where the introns may be removed byalternative splicing. Furthermore it should be noted that differentspecies of mRNAs encoded by the same genomic sequence can exist atvarying levels in a cell, and detection of these various levels of mRNAspecies can be indicative of differential expression of the encoded geneproduct in the cell.

A genomic sequence of interest comprises the nucleic acid presentbetween the initiation codon and the stop codon, as defined in thelisted sequences, including all of the introns that are normally presentin a native chromosome. It can further include the 3′ and 5′untranslated regions found in the mature mRNA. It can further includespecific transcriptional and translational regulatory sequences, such aspromoters, enhancers, etc., including about 1 kb, but possibly more, offlanking genomic DNA at either the 5′ and 3′ end of the transcribedregion. The genomic DNA can be isolated as a fragment of 100 kbp orsmaller; and substantially free of flanking chromosomal sequence. Thegenomic DNA flanking the coding region, either 3′ and 5′, or internalregulatory sequences as sometimes found in introns, contains sequencesrequired for proper tissue, stage-specific, or disease-state specificexpression.

The nucleic acid compositions of the subject invention can encode all ora part of the naturally-occurring polypeptides. Double or singlestranded fragments can be obtained from the DNA sequence by chemicallysynthesizing oligonucleotides in accordance with conventional methods,by restriction enzyme digestion, by PCR amplification, etc.

Probes specific to the polynucleotides described herein can be generatedusing the polynucleotide sequences disclosed herein. The probes areusually a fragment of a polynucleotide sequences provided herein. Theprobes can be synthesized chemically or can be generated from longerpolynucleotides using restriction enzymes. The probes can be labeled,for example, with a radioactive, biotinylated, or fluorescent tag.Preferably, probes are designed based upon an identifying sequence ofany one of the polynucleotide sequences provided herein. Morepreferably, probes are designed based on a contiguous sequence of one ofthe subject polynucleotides that remain unmasked following applicationof a masking program for masking low complexity (e.g., XBLAST,RepeatMasker, etc.) to the sequence, i.e., one would select an unmaskedregion, as indicated by the polynucleotides outside the poly-n stretchesof the masked sequence produced by the masking program.

The polynucleotides of interest in the subject invention are isolatedand obtained in substantial purity, generally as other than an intactchromosome. Usually, the polynucleotides, either as DNA or RNA, will beobtained substantially free of other naturally-occurring nucleic acidsequences that they are usually associated with, generally being atleast about 50%, usually at least about 90% pure and are typically“recombinant”, e.g., flanked by one or more nucleotides with which it isnot normally associated on a naturally occurring chromosome.

The polynucleotides described herein can be provided as a linearmolecule or within a circular molecule, and can be provided withinautonomously replicating molecules (vectors) or within molecules withoutreplication sequences. Expression of the polynucleotides can beregulated by their own or by other regulatory sequences known in theart. The polynucleotides can be introduced into suitable host cellsusing a variety of techniques available in the art, such as transferrinpolycation-mediated DNA transfer, transfection with naked orencapsulated nucleic acids, liposome-mediated DNA transfer,intracellular transportation of DNA-coated latex beads, protoplastfusion, viral infection, electroporation, gene gun, calciumphosphate-mediated transfection, and the like.

The nucleic acid compositions described herein can be used to, forexample, produce polypeptides, as probes for the detection of mRNA inbiological samples (e.g., extracts of human cells) or cDNA produced fromsuch samples, to generate additional copies of the polynucleotides, togenerate ribozymes or antisense oligonucleotides, and as single strandedDNA probes or as triple-strand forming oligonucleotides. The probesdescribed herein can be used to, for example, determine the presence orabsence of any one of the polynucleotide provided herein or variantsthereof in a sample. These and other uses are described in more detailbelow.

Polypeptides and Variants Thereof

The present invention further provides polypeptides encoded bypolynucleotides that represent genes that are differentially expressedin cancer cells. Such polypeptides are referred to herein as“polypeptides associated with cancer.” The polypeptides can be used togenerate antibodies specific for a polypeptide associated with cancer,which antibodies are in turn useful in diagnostic methods, prognosticsmethods, therametric methods, and the like as discussed in more detailherein. Polypeptides are also useful as targets for therapeuticintervention, as discussed in more detail herein.

The polypeptides contemplated by the invention include those encoded bythe disclosed polynucleotides and the genes to which thesepolynucleotides correspond, as well as nucleic acids that, by virtue ofthe degeneracy of the genetic code, are not identical in sequence to thedisclosed polynucleotides. Further polypeptides contemplated by theinvention include polypeptides that are encoded by polynucleotides thathybridize to polynucleotide of the sequence listing. Thus, the inventionincludes within its scope a polypeptide encoded by a polynucleotidehaving the sequence of any one of the polynucleotide sequences providedherein, or a variant thereof.

In general, the term “polypeptide” as used herein refers to both thefull length polypeptide encoded by the recited polynucleotide, thepolypeptide encoded by the gene represented by the recitedpolynucleotide, as well as portions or fragments thereof. “Polypeptides”also includes variants of the naturally occurring proteins, where suchvariants are homologous or substantially similar to the naturallyoccurring protein, and can be of an origin of the same or differentspecies as the naturally occurring protein (e.g., human, murine, or someother species that naturally expresses the recited polypeptide, usuallya mammalian species). In general, variant polypeptides have a sequencethat has at least about 80%, usually at least about 90%, and moreusually at least about 98% sequence identity with a differentiallyexpressed polypeptide described herein, as measured by BLAST 2.0 usingthe parameters described above. The variant polypeptides can benaturally or non-naturally glycosylated, i.e., the polypeptide has aglycosylation pattern that differs from the glycosylation pattern foundin the corresponding naturally occurring protein.

The invention also encompasses homologs of the disclosed polypeptides(or fragments thereof) where the homologs are isolated from otherspecies, i.e. other animal or plant species, where such homologs,usually mammalian species, e.g. rodents, such as mice, rats; domesticanimals, e.g., horse, cow, dog, cat; and humans. By “homolog” is meant apolypeptide having at least about 35%, usually at least about 40% andmore usually at least about 60% amino acid sequence identity to aparticular differentially expressed protein as identified above, wheresequence identity is determined using the BLAST 2.0 algorithm, with theparameters described supra.

In general, the polypeptides of interest in the subject invention areprovided in a non-naturally occurring environment, e.g. are separatedfrom their naturally occurring environment. In certain embodiments, thesubject protein is present in a composition that is enriched for theprotein as compared to a cell or extract of a cell that naturallyproduces the protein. As such, isolated polypeptide is provided, whereby “isolated” or “in substantially isolated form” is meant that theprotein is present in a composition that is substantially free of otherpolypeptides, where by substantially free is meant that less than 90%,usually less than 60% and more usually less than 50% of the compositionis made up of other polypeptides of a cell that the protein is naturallyfound.

Also within the scope of the invention are variants; variants ofpolypeptides include mutants, fragments, and fusions. Mutants caninclude amino acid substitutions, additions or deletions. The amino acidsubstitutions can be conservative amino acid substitutions orsubstitutions to eliminate non-essential amino acids, such as to alter aglycosylation site, a phosphorylation site or an acetylation site, or tominimize misfolding by substitution or deletion of one or more cysteineresidues that are not necessary for function. Conservative amino acidsubstitutions are those that preserve the general charge,hydrophobicity/hydrophilicity, and/or steric bulk of the amino acidsubstituted.

Variants can be designed so as to retain or have enhanced biologicalactivity of a particular region of the protein (e.g., a functionaldomain and/or, where the polypeptide is a member of a protein family, aregion associated with a consensus sequence). For example, muteins canbe made which are optimized for increased antigenicity, i.e. amino acidvariants of a polypeptide may be made that increase the antigenicity ofthe polypeptide. Selection of amino acid alterations for production ofvariants can be based upon the accessibility (interior vs. exterior) ofthe amino acid (see, e.g., Go et al, Int. J. Peptide Protein Res. (1980)15:211), the thermostability of the variant polypeptide (see, e.g.,Querol et al., Prot. Eng. (1996) 9:265), desired glycosylation sites(see, e.g., Olsen and Thomsen, J. Gen. Microbiol. (1991) 137:579),desired disulfide bridges (see, e.g., Clarke et al., Biochemistry (1993)32:4322; and Wakarchuk et al., Protein Eng. (1994) 7:1379), desiredmetal binding sites (see, e.g., Toma et al., Biochemistry (1991) 30:97,and Haezerbrouck et al., Protein Eng. (1993) 6:643), and desiredsubstitutions with in proline loops (see, e.g., Masul et al., Appl. Env.Microbiol. (1994) 60:3579). Cysteine-depleted muteins can be produced asdisclosed in U.S. Pat. No. 4,959,314. Variants also include fragments ofthe polypeptides disclosed herein, particularly biologically activefragments and/or fragments corresponding to functional domains.Fragments of interest will typically be at least about 10 aa to at leastabout 15 aa in length, usually at least about 50 aa in length, and canbe as long as 300 aa in length or longer, but will usually not exceedabout 1000 aa in length, where the fragment will have a stretch of aminoacids that is identical to a polypeptide encoded by a polynucleotidehaving a sequence of any one of the polynucleotide sequences providedherein, or a homolog thereof. The protein variants described herein areencoded by polynucleotides that are within the scope of the invention.The genetic code can be used to select the appropriate codons toconstruct the corresponding variants.

A fragment of a subject polypeptide is, for example, a polypeptidehaving an amino acid sequence which is a portion of a subjectpolypeptide e.g. a polypeptide encoded by a subject polynucleotide thatis identified by any one of the sequence of SEQ ID NOS: 1-13996 or itscomplement. The polypeptide fragments of the invention are preferably atleast about 9 aa, at least about 15 aa, and more preferably at leastabout 20 aa, still more preferably at least about 30 aa, and even morepreferably, at least about 40 aa, at least about 50 aa, at least about75 aa, at least about 100 aa, at least about 125 aa or at least about150 aa in length. A fragment “at least 20 aa in length,” for example, isintended to include 20 or more contiguous amino acids from, for example,the polypeptide encoded by a cDNA, in a cDNA clone contained in adeposited library, or a nucleotide sequence shown in SEQ ID NOS: 1-13996or the complementary stand thereof. In this context “about” includes theparticularly recited value or a value larger or smaller by several (5,4, 3, 2, or 1) amino acids. These polypeptide fragments have uses thatinclude, but are not limited to, production of antibodies as discussedherein. Of course, larger fragments (e.g., at least 150, 175, 200, 250,500, 600, 1000, or 2000 amino acids in length) are also encompassed bythe invention.

Moreover, representative examples of polypeptides fragments of theinvention (useful in, for example, as antigens for antibody production),include, for example, fragments comprising, or alternatively consistingof, a sequence from about amino acid number 1-10, 5-10, 10-20, 21-31,31-40, 41-61, 61-81, 91-120, 121-140, 141-162, 162-200, 201-240,241-280, 281-320, 321-360, 360-400, 400-450, 451-500, 500-600, 600-700,700-800, 800-900 and the like. In this context “about” includes theparticularly recited range or a range larger or smaller by several (5,4, 3, 2, or 1) amino acids, at either terminus or at both termini. Insome embodiments, these fragments has a functional activity (e.g.,biological activity) whereas in other embodiments, these fragments maybe used to make an antibody.

In one example, a polynucleotide having a sequence set forth in thesequence listing, containing no flanking sequences (i.e., consisting ofthe sequence set forth in the sequence listing), may be cloned into anexpression vector having ATG and a stop codon (e.g. any one of the pETvector from Invitrogen, or other similar vectors from othermanufactures), and used to express a polypeptide of interest encoded bythe polynucleotide in a suitable cell, e.g., a bacterial cell.Accordingly, the polynucleotides may be used to produce polypeptides,and these polypeptides may be used to produce antibodies by knownmethods described above and below. In many embodiments, the sequence ofthe encoded polypeptide does not have to be known prior to itsexpression in a cell. However, if it desirable to know the sequence ofthe polypeptide, this may be derived from the sequence of thepolynucleotide. Using the genetic code, the polynucleotide may betranslated by hand, or by computer means. Suitable software foridentifying open reading frames and translating them into polypeptidesequences are well know in the art, and include: Lasergene™ from DNAStar(Madison, Wis.), and Vector NTI™ from Informax (Frederick Md.), and thelike.

Further polypeptide variants may are described in PCT publicationsWO/00-55173, WO/01-07611 and WO/02-16429

Vectors, Host Cells and Protein Production

The present invention also relates to vectors containing thepolynucleotide of the present invention, host cells, and the productionof polypeptides by recombinant techniques. The vector may be, forexample, a phage, plasmid, viral, or retroviral vector. Retroviralvectors may be replication competent or replication defective. In thelatter case, viral propagation generally will occur only incomplementing host cells.

The polynucleotides of the invention may be joined to a vectorcontaining a selectable marker for propagation in a host. Generally, aplasmid vector is introduced in a precipitate, such as a calciumphosphate precipitate, or in a complex with a charged lipid. If thevector is a virus, it may be packaged in vitro using an appropriatepackaging cell line and then transduced into host cells.

The polynucleotide insert should be operatively linked to an appropriatepromoter, such as the phage lambda PL promoter, the E. coli lac, trp,phoA and tac promoters, the SV40 early and late promoters and promotersof retroviral LTRs, to name a few. Other suitable promoters will beknown to the skilled artisan. The expression constructs will furthercontain sites for transcription initiation, termination, and, in thetranscribed region, a ribosome binding site for translation. The codingportion of the transcripts expressed by the constructs will preferablyinclude a translation initiating codon at the beginning and atermination codon (UAA, UGA or UAG) appropriately positioned at the endof the polypeptide to be translated.

As indicated, the expression vectors will preferably include at leastone selectable marker. Such markers include dihydrofolate reductase,G418 or neomycin resistance for eukaryotic cell culture andtetracycline, kanamycin or ampicillin resistance genes for culturing inE. coli and other bacteria.

Representative examples of appropriate hosts include, but are notlimited to, bacterial cells, such as E. coli, Streptomyces andSalmonella typhimurium cells; fungal cells, such as yeast cells (e.g.,Saccharomyces cerevisiae or Pichia pastoris (ATCC Accession No.201178)); insect cells such as Drosophila S2 and Spodoptera Sf9 cells;animal cells such as CHO, COS, 293, and Bowes melanoma cells; and plantcells. Appropriate culture mediums and conditions for theabove-described host cells are known in the art.

Among vectors preferred for use in bacteria include pQE70, pQE60 andpQE-9, available from QIAGEN, Inc.; pBluescript vectors, Phagescriptvectors, pNHSA, pNH16a, pNH18A, pNH46A, available from StratageneCloning Systems, Inc.; and ptrc99a, pKK223-3, pKK233-3, pDR540, pRITSavailable from Pharmacia Biotech, Inc. Among preferred eukaryoticvectors are pWLNEO, pSV2CAT, pOG44, pXT1 and pSG available fromStratagene; and pSVK3, pBPV, pMSG and pSVL available from Pharmacia.Preferred expression vectors for use in yeast systems include, but arenot limited to pYES2, pYD1, pTEF1/Zeo, pYES2/GS, pPICZ, pGAPZ,pGAPZalph, pPIC9, pPIC3.5, pHIL-D2, pHIL-S1, pPIC3.5K, pPIC9K, andPAO815 (all available from Invitrogen, Carload, Calif.). Other suitablevectors will be readily apparent to the skilled artisan.

Nucleic acids of interest may be cloned into a suitable vector by routemethods. Suitable vectors include plasmids, cosmids, recombinant viralvectors e.g. retroviral vectors, YACs, BACs and the like, phage vectors.

Introduction of the construct into the host cell can be effected bycalcium phosphate transfection, DEAE-dextran mediated transfection,cationic lipid-mediated transfection, electroporation, transduction,infection, or other methods. Such methods are described in many standardlaboratory manuals, such as Davis et al., Basic Methods In MolecularBiology (1986). It is specifically contemplated that the polypeptides ofthe present invention may in fact be expressed by a host cell lacking arecombinant vector.

A polypeptide of this invention can be recovered and purified fromrecombinant cell cultures by well-known methods including ammoniumsulfate or ethanol precipitation, acid extraction, anion or cationexchange chromatography, phosphocellulose chromatography, hydrophobicinteraction chromatography, affinity chromatography, hydroxylapatitechromatography and lectin chromatography. Most preferably, highperformance liquid chromatography (“HPLC”) is employed for purification.

Polypeptides of the present invention can also be recovered from:products purified from natural sources, including bodily fluids, tissuesand cells, whether directly isolated or cultured; products of chemicalsynthetic procedures; and products produced by recombinant techniquesfrom a prokaryotic or eukaryotic host, including, for example,bacterial, yeast higher plant, insect, and mammalian cells. Dependingupon the host employed in a recombinant production procedure, thepolypeptides of the present invention may be glycosylated or may benon-glycosylated. In addition, polypeptides of the invention may alsoinclude an initial modified methionine residue, in some cases as aresult of host mediated processes. Thus, it is well known in the artthat the N-terminal methionine encoded by the translation initiationcodon generally is removed with high efficiency from any protein aftertranslation in all eukaryotic cells. While the N-terminal methionine onmost proteins also is efficiently removed in most prokaryotes, for someproteins, this prokaryotic removal process is inefficient, depending onthe nature of the amino acid to which the N-terminal methionine iscovalently linked.

Suitable methods and compositions for polypeptide expression may befound in PCT publications WO/00-55173, WO/01-07611 and WO/02-16429, andsuitable methods and compositions for production of modifiedpolypeptides may be found in PCT publications WO/00-55173, WO/01-07611and WO/02-16429.

Antibodies and Other Polypeptide or Polynucleotide Binding Molecules

The present invention further provides antibodies, which may be isolatedantibodies, that are specific for a polypeptide encoded by apolynucleotide described herein and/or a polypeptide of a gene thatcorresponds to a polynucleotide described herein. Antibodies can beprovided in a composition comprising the antibody and a buffer and/or apharmaceutically acceptable excipient. Antibodies specific for apolypeptide associated with cancer are useful in a variety of diagnosticand therapeutic methods, as discussed in detail herein.

Gene products, including polypeptides, mRNA (particularly mRNAs havingdistinct secondary and/or tertiary structures), cDNA, or complete gene,can be prepared and used for raising antibodies for experimental,diagnostic, and therapeutic purposes. Antibodies may be used to identifya gene corresponding to a polynucleotide. The polynucleotide or relatedcDNA is expressed as described above, and antibodies are prepared. Theseantibodies are specific to an epitope on the polypeptide encoded by thepolynucleotide, and can precipitate or bind to the corresponding nativeprotein in a cell or tissue preparation or in a cell-free extract of anin vitro expression system.

Antibodies

Further polypeptides of the invention relate to antibodies and T-cellantigen receptors (TCR) which immunospecifically bind a subjectpolypeptide, subject polypeptide fragment, or variant thereof, and/or anepitope thereof (as determined by immunoassays well known in the art forassaying specific antibody-antigen binding). Antibodies of the inventioninclude, but are not limited to, polyclonal, monoclonal, multispecific,human, humanized or chimeric antibodies, single chain antibodies, Fabfragments, F(ab′) fragments, fragments produced by a Fab expressionlibrary, anti-idiotypic (anti-Id) antibodies (including, e.g., anti-Idantibodies to antibodies of the invention), and epitope-bindingfragments of any of the above. The term “antibody,” as used herein,refers to immunoglobulin molecules and immunologically active portionsof immunoglobulin molecules, i.e., molecules that contain an antigenbinding site that immunospecifically binds an antigen. Theimmunoglobulin molecules of the invention can be of any type (e.g., IgG,IgE, IgM, IgD, IgA and IgY), class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1and IgA2) or subclass of immunoglobulin molecule.

Most preferably the antibodies are human antigen-binding antibodyfragments of the present invention and include, but are not limited to,Fab. Fab′ and F(ab′)₂, Fd, single-chain Fvs (scFv), single-chainantibodies, disulfide-linked Fvs (sdFv) and fragments comprising eithera V_(L) or V_(H) domain. Antigen-binding antibody fragments, includingsingle-chain antibodies, may comprise the variable region(s) alone or incombination with the entirety or a portion of the following: hingeregion, C_(H)1, C_(H)2, and C_(H)3 domains. Also included in theinvention are antigen-binding fragments also comprising any combinationof variable region(s) with a hinge region, C_(H)1, C_(H)2, and C_(H)3domains. The antibodies of the invention may be from any animal originincluding birds and mammals. Preferably, the antibodies are human,murine (e.g., mouse and rat), donkey, ship rabbit, goat, guinea pig,camel, horse, or chicken. As used herein, “human” antibodies includeantibodies having the amino acid sequence of a human immunoglobulin andinclude antibodies isolated from, human immunoglobulin libraries or fromanimals transgenic for one or more human immunoglobulin and that do notexpress endogenous immunoglobulins, as described infra and, for examplein, U.S. Pat. No. 5,939,598 by Kucherlapati et al.

The antibodies of the present invention may be monospecific, bispecific,trispecific or of greater multispecificity. Multispecific antibodies maybe specific for different epitopes of a polypeptide of the presentinvention or may be specific for both a polypeptide of the presentinvention as well as for a heterologous epitope, such as a heterologouspolypeptide or solid support material. See, e.g., PCT publications WO93/17715; WO 92/08802; WO 91/00360; WO 92/05793; Tutt, et al., J.Immunol. 147:60-69 (1991); U.S. Pat. Nos. 4,474,893; 4,714,681;4,925,648; 5,573,920; 5,601,819; Kostelny et al., J. Immunol.148:1547-1553 (1992).

Antibodies of the present invention may be described or specified interms of the epitope(s) or portion(s) of a polypeptide of the presentinvention which they recognize or specifically bind. The epitope(s) orpolypeptide portion(s) may be specified as described herein, e.g., byN-terminal and C-terminal positions, or by size in contiguous amino acidresidues. Antibodies which specifically bind any epitope or polypeptideof the present invention may also be excluded. Therefore, the presentinvention includes antibodies that specifically bind polypeptides of thepresent invention, and allows for the exclusion of the same.

Antibodies of the present invention may also be described or specifiedin terms of their cross-reactivity. Antibodies that do not bind anyother analog, ortholog, or homolog of a polypeptide of the presentinvention are included. Antibodies that bind polypeptides with at least95%, at least 90%, at least 85%, at least 80%, at least 75%, at least70%, at least 65%, at least 60%, at least 55%, and at least 50% identity(as calculated using methods known in the art and described herein) to apolypeptide of the present invention are also included in the presentinvention. In specific embodiments, antibodies of the present inventioncross-react with murine, rat and/or rabbit homologs of human proteinsand the corresponding epitopes thereof. Antibodies that do not bindpolypeptides with less than 95%, less than 90%, less than 85%, less than80%, less than 75%, less than 70%, less than 65%, less than 60%, lessthan 55%, and less than 50% identity (as calculated using methods knownin the art and described herein) to a polypeptide of the presentinvention are also included in the present invention. In a specificembodiment, the above-described cross-reactivity is with respect to anysingle specific antigenic or immunogenic polypeptide, or combination(s)of 2, 3, 4, 5, or more of the specific antigenic and/or immunogenicpolypeptides disclosed herein. Further included in the present inventionare antibodies which bind polypeptides encoded by polynucleotides whichhybridize to a polynucleotide of the present invention under stringenthybridization conditions (as described herein). Antibodies of thepresent invention may also be described or specified in terms of theirbinding affinity to a polypeptide of the invention. Preferred bindingaffinities include those with a dissociation constant or Kd less 5×10⁻⁵M, 10⁻⁵ M, 5×10⁻⁶ M, 10⁻⁶M, 5×10⁻⁷ M, 10⁻⁷ M, 5×10⁻⁸ M, 10⁻⁸M, 5×10⁻⁹ M,10 M, 5×10⁻¹⁰ M, 10⁻¹⁰ M, etc.

The invention also provides antibodies that competitively inhibitbinding of an antibody to an epitope of the invention as determined byany method known in the art for determining competitive binding, forexample, the immunoassays described herein. In preferred embodiments,the antibody competitively inhibits binding to the epitope by at least95%, at least 90%, at least 85%, at least 80%, at least 75%, at least70%, at least 60%, or at least 50%.

Methods for making screening, assaying, humanizing, and modifyingdifferent types of antibody are well known in the art and may be foundin PCT publications WO/00-55173, WO/01-07611 and WO/02-16429.

In addition, the invention further provides polynucleotides comprising anucleotide sequence encoding an antibody of the invention and fragmentsthereof. The invention also encompasses polynucleotides that hybridizeunder stringent or alternatively, under lower stringency hybridizationconditions, e.g., as defined supra, to polynucleotides that encode anantibody, preferably, that specifically binds to a polypeptide of theinvention, preferably, an antibody that binds to a subject polypeptide.

The antibodies of the invention can be produced by any method known inthe art for the synthesis of antibodies, in particular, by chemicalsynthesis or preferably, by recombinant expression techniques.Recombinant expression of an antibody of the invention, or fragment,derivative or analog thereof, (e.g., a heavy or light chain of anantibody of the invention or a single chain antibody of the invention),requires construction of an expression vector containing apolynucleotide that encodes the antibody. Once a polynucleotide encodingan antibody molecule or a heavy or light chain of an antibody, orportion thereof (preferably containing the heavy or light chain variabledomain), of the invention has been obtained, the vector for theproduction of the antibody molecule may be produced by recombinant DNAtechnology using techniques well known in the art. Thus, methods forpreparing a protein by expressing a polynucleotide containing anantibody encoding nucleotide sequence are described herein. Methodswhich are well known to those skilled in the art can be used toconstruct expression vectors containing antibody coding sequences andappropriate transcriptional and translational control signals. Thesemethods include, for example, in vitro recombinant DNA techniques,synthetic techniques, and in vivo genetic recombination. The invention,thus, provides replicable vectors comprising a nucleotide sequenceencoding an antibody molecule of the invention, or a heavy or lightchain thereof, or a heavy or light chain variable domain, operablylinked to a promoter. Such vectors may include the nucleotide sequenceencoding the constant region of the antibody molecule (see, e.g., PCTPublication WO 86/05807; PCT Publication WO 89/01036; and U.S. Pat. No.5,122,464) and the variable domain of the antibody may be cloned intosuch a vector for expression of the entire heavy or light chain.

The expression vector is transferred to a host cell by conventionaltechniques and the transfected cells are then cultured by conventionaltechniques to produce an antibody of the invention. Thus, the inventionincludes host cells containing a polynucleotide encoding an antibody ofthe invention, or a heavy or light chain thereof, or a single chainantibody of the invention, operably linked to a heterologous promoter.In preferred embodiments for the expression of double-chainedantibodies, vectors encoding both the heavy and light chains may beco-expressed in the host cell for expression of the entireimmunoglobulin molecule, as detailed below.

A variety of host-expression vector systems may be utilized to expressthe antibody molecules of the invention. Such host-expression systemsrepresent vehicles by which the coding sequences of interest may beproduced and subsequently purified, but also represent cells which may,when transformed or transfected with the appropriate nucleotide codingsequences, express an antibody molecule of the invention in situ. Theseinclude but are not limited to microorganisms such as bacteria (e.g., E.coli, B. subtilis) transformed with recombinant bacteriophage DNA,plasmid DNA or cosmid DNA expression vectors containing antibody codingsequences; yeast (e.g., Saccharomyces, Pichia) transformed withrecombinant yeast expression vectors containing antibody codingsequences; insect cell systems infected with recombinant virusexpression vectors (e.g., baculovirus) containing antibody codingsequences; plant cell systems infected with recombinant virus expressionvectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus,TMV) or transformed with recombinant plasmid expression vectors (e.g.,Ti plasmid) containing antibody coding sequences; or mammalian cellsystems (e.g., COS, CHO, BHK, 293, 3T3 cells) harboring recombinantexpression constructs containing promoters derived from the genome ofmammalian cells (e.g., metallothionein promoter) or from mammalianviruses (e.g., the adenovirus late promoter; the vaccinia virus 7.5Kpromoter). Preferably, bacterial cells such as Escherichia coli, andmore preferably, eukaryotic cells, especially for the expression ofwhole recombinant antibody molecule, are used for the expression of arecombinant antibody molecule. For example, mammalian cells such asChinese hamster ovary cells (CHO), in conjunction with a vector such asthe major intermediate early gene promoter element from humancytomegalovirus is an effective expression system for antibodies(Foecking et al., Gene 45:101 (1986); Cockett et al., Bio/Technology 8:2(1990)).

Antibodies production is well known in the art. Exemplary methods andcompositions for making antibodies may be found in PCT publicationsWO/00-55173, WO/01-07611 and WO/02-16429.

Immunophenotyping

The antibodies of the invention may be utilized for immunophenotyping ofcell lines and biological samples. The translation product of the geneof the present invention may be useful as a cell specific marker, ormore specifically as a cellular marker that is differentially expressedat various stages of differentiation and/or maturation of particularcell types. Monoclonal antibodies directed against a specific epitope,or combination of epitopes, will allow for the screening of cellularpopulations expressing the marker. Various techniques can be utilizedusing monoclonal antibodies to screen for cellular populationsexpressing the marker(s), and include magnetic separation usingantibody-coated magnetic beads, “panning” with antibody attached to asolid matrix (i.e., plate), and flow cytometry (See, e.g., U.S. Pat. No.5,985,660; and Morrison et al. Cell, 96:737-49 (1999)).

These techniques allow for the screening of particular populations ofcells, such as might be found with hematological malignancies (i.e.minimal residual disease (MRD) in acute leukemic patients) and “non-selfcells in transplantations to prevent Graft-versus-Host Disease (GVHD).Alternatively, these techniques allow for the screening of hematopoieticstem and progenitor cells capable of undergoing proliferation and/ordifferentiation, as might be found in human umbilical cord blood.

Kits

Also provided by the subject invention are kits for practicing thesubject methods, as described above. The subject kits include at leastone or more of: a subject nucleic acid, isolated polypeptide or anantibody thereto. Other optional components of the kit include:restriction enzymes, control primers and plasmids; buffers, cells,carriers adjuvents etc. The nucleic acids of the kit may also haverestrictions sites, multiple cloning sites, primer sites, etc tofacilitate their ligation other plasmids. The various components of thekit may be present in separate containers or certain compatiblecomponents may be precombined into a single container, as desired. Inmany embodiments, kits with unit doses of the active agent, e.g. in oralor injectable doses, are provided. In certain embodiments, controls,such as samples from a cancerous or non-cancerous cell are provided bythe invention. Further embodiments of the kit include an antibody for asubject polypeptide and a chemotherapeutic agent to be used incombination with the polypeptide as a treatment.

In addition to above-mentioned components, the subject kits typicallyfurther include instructions for using the components of the kit topractice the subject methods. The instructions for practicing thesubject methods are generally recorded on a suitable recording medium.For example, the instructions may be printed on a substrate, such aspaper or plastic, etc. As such, the instructions may be present in thekits as a package insert, in the labeling of the container of the kit orcomponents thereof (i.e., associated with the packaging or subpackaging)etc. In other embodiments, the instructions are present as an electronicstorage data file present on a suitable computer readable storagemedium, e.g. CD-ROM, diskette, etc. In yet other embodiments, the actualinstructions are not present in the kit, but means for obtaining theinstructions from a remote source, e.g. via the internet, are provided.An example of this embodiment is a kit that includes a web address wherethe instructions can be viewed and/or from which the instructions can bedownloaded. As with the instructions, this means for obtaining theinstructions is recorded on a suitable substrate.

Computer-Related Embodiments

In general, a library of polynucleotides is a collection of sequenceinformation, which information is provided in either biochemical form(e.g., as a collection of polynucleotide molecules), or in electronicform (e.g., as a collection of polynucleotide sequences stored in acomputer-readable form, as in a computer system and/or as part of acomputer program). The sequence information of the polynucleotides canbe used in a variety of ways, e.g., as a resource for gene discovery, asa representation of sequences expressed in a selected cell type (e.g.,cell type markers), and/or as markers of a given disease or diseasestate. For example, in the instant case, the sequences ofpolynucleotides and polypeptides corresponding to genes differentiallyexpressed in cancer, as well as the nucleic acid and amino acidsequences of the genes themselves, can be provided in electronic form ina computer database.

In general, a disease marker is a representation of a gene product thatis present in all cells affected by disease either at an increased ordecreased level relative to a normal cell (e.g., a cell of the same orsimilar type that is not substantially affected by disease). Forexample, a polynucleotide sequence in a library can be a polynucleotidethat represents an mRNA, polypeptide, or other gene product encoded bythe polynucleotide, that is either overexpressed or underexpressed in acancerous cell affected by cancer relative to a normal (i.e.,substantially disease-free) cell.

The nucleotide sequence information of the library can be embodied inany suitable form, e.g., electronic or biochemical forms. For example, alibrary of sequence information embodied in electronic form comprises anaccessible computer data file (or, in biochemical form, a collection ofnucleic acid molecules) that contains the representative nucleotidesequences of genes that are differentially expressed (e.g.,overexpressed or underexpressed) as between, for example, i) a cancerouscell and a normal cell; ii) a cancerous cell and a dysplastic cell; iii)a cancerous cell and a cell affected by a disease or condition otherthan cancer; iv) a metastatic cancerous cell and a normal cell and/ornon-metastatic cancerous cell; v) a malignant cancerous cell and anon-malignant cancerous cell (or a normal cell) and/or vi) a dysplasticcell relative to a normal cell. Other combinations and comparisons ofcells affected by various diseases or stages of disease will be readilyapparent to the ordinarily skilled artisan. Biochemical embodiments ofthe library include a collection of nucleic acids that have thesequences of the genes in the library, where the nucleic acids cancorrespond to the entire gene in the library or to a fragment thereof,as described in greater detail below.

The polynucleotide libraries of the subject invention generally comprisesequence information of a plurality of polynucleotide sequences, whereat least one of the polynucleotides has a sequence of any of sequencedescribed herein. By plurality is meant at least 2, usually at least 3and can include up to all of the sequences described herein. The lengthand number of polynucleotides in the library will vary with the natureof the library, e.g., if the library is an oligonucleotide array, a cDNAarray, a computer database of the sequence information, etc.

Where the library is an electronic library, the nucleic acid sequenceinformation can be present in a variety of media. “Media” refers to amanufacture, other than an isolated nucleic acid molecule, that containsthe sequence information of the present invention. Such a manufactureprovides the genome sequence or a subset thereof in a form that can beexamined by means not directly applicable to the sequence as it existsin a nucleic acid. For example, the nucleotide sequence of the presentinvention, e.g. the nucleic acid sequences of any of the polynucleotidesof the sequences described herein, can be recorded on computer readablemedia, e.g. any medium that can be read and accessed directly by acomputer. Such media include, but are not limited to: magnetic storagemedia, such as a floppy disc, a hard disc storage medium, and a magnetictape; optical storage media such as CD-ROM; electrical storage mediasuch as RAM and ROM; and hybrids of these categories such asmagnetic/optical storage media.

One of skill in the art can readily appreciate how any of the presentlyknown computer readable mediums can be used to create a manufacturecomprising a recording of the present sequence information. “Recorded”refers to a process for storing information on computer readable medium,using any such methods as known in the art. Any convenient data storagestructure can be chosen, based on the means used to access the storedinformation. A variety of data processor programs and formats can beused for storage, e.g. word processing text file, database format, etc.In addition to the sequence information, electronic versions oflibraries comprising one or more sequence described herein can beprovided in conjunction or connection with other computer-readableinformation and/or other types of computer-readable files (e.g.,searchable files, executable files, etc, including, but not limited to,for example, search program software, etc.).

By providing the nucleotide sequence in computer readable form, theinformation can be accessed for a variety of purposes. Computer softwareto access sequence information (e.g. the NCBI sequence database) ispublicly available. For example, the gapped BLAST (Altschul et al.,Nucleic Acids Res. (1997) 25:3389-3402) and BLAZE (Brutlag et al., Comp.Chem. (1993) 17:203) search algorithms on a Sybase system, or theTeraBLAST (TimeLogic, Crystal Bay, Nev.) program optionally running on aspecialized computer platform available from TimeLogic, can be used toidentify open reading frames (ORFs) within the genome that containhomology to ORFs from other organisms.

As used herein, “a computer-based system” refers to the hardware means,software means, and data storage means used to analyze the nucleotidesequence information of the present invention. The minimum hardware ofthe computer-based systems of the present invention comprises a centralprocessing unit (CPU), input means, output means, and data storagemeans. A skilled artisan can readily appreciate that any one of thecurrently available computer-based system are suitable for use in thepresent invention. The data storage means can comprise any manufacturecomprising a recording of the present sequence information as describedabove, or a memory access means that can access such a manufacture.

“Search means” refers to one or more programs implemented on thecomputer-based system, to compare a target sequence or target structuralmotif, or expression levels of a polynucleotide in a sample, with thestored sequence information. Search means can be used to identifyfragments or regions of the genome that match a particular targetsequence or target motif. A variety of known algorithms are publiclyknown and commercially available, e.g. MacPattern (EMBL), TeraBLAST(TimeLogic), BLASTN and BLASTX (NCBI). A “target sequence” can be anypolynucleotide or amino acid sequence of six or more contiguousnucleotides or two or more amino acids, preferably from about 10 to 100amino acids or from about 30 to 300 nt. A variety of means for comparingnucleic acids or polypeptides may be used to compare accomplish asequence comparison (e.g., to analyze target sequences, target motifs,or relative expression levels) with the data storage means. A skilledartisan can readily recognize that any one of the publicly availablehomology search programs can be used to search the computer basedsystems of the present invention to compare of target sequences andmotifs. Computer programs to analyze expression levels in a sample andin controls are also known in the art.

A “target structural motif,” or “target motif,” refers to any rationallyselected sequence or combination of sequences in which the sequence(s)are chosen based on a three-dimensional configuration that is formedupon the folding of the target motif, or on consensus sequences ofregulatory or active sites. There are a variety of target motifs knownin the art. Protein target motifs include, but are not limited to,enzyme active sites and signal sequences, kinase domains, receptorbinding domains, SH2 domains, SH3 domains, phosphorylation sites,protein interaction domains, transmembrane domains, etc. Nucleic acidtarget motifs include, but are not limited to, hairpin structures,promoter sequences and other expression elements such as binding sitesfor transcription factors.

A variety of structural formats for the input and output means can beused to input and output the information in the computer-based systemsof the present invention. One format for an output means ranks therelative expression levels of different polynucleotides. Suchpresentation provides a skilled artisan with a ranking of relativeexpression levels to determine a gene expression profile. A geneexpression profile can be generated from, for example, a cDNA libraryprepared from mRNA isolated from a test cell suspected of beingcancerous or pre-cancerous, comparing the sequences or partial sequencesof the clones against the sequences in an electronic database, where thesequences of the electronic database represent genes differentiallyexpressed in a cancerous cell, e.g., a cancerous breast cell. The numberof clones having a sequence that has substantial similarity to asequence that represents a gene differentially expressed in a cancerouscell is then determined, and the number of clones corresponding to eachof such genes is determined. An increased number of clones thatcorrespond to differentially expressed gene is present in the cDNAlibrary of the test cell (relative to, for example, the number of clonesexpected in a cDNA of a normal cell) indicates that the test cell iscancerous.

As discussed above, the “library” as used herein also encompassesbiochemical libraries of the polynucleotides of the sequences describedherein, e.g., collections of nucleic acids representing the providedpolynucleotides. The biochemical libraries can take a variety of forms,e.g., a solution of cDNAs, a pattern of probe nucleic acids stablyassociated with a surface of a solid support (i.e., an array) and thelike. Of particular interest are nucleic acid arrays in which one ormore of the genes described herein is represented by a sequence on thearray. By array is meant an article of manufacture that has at least asubstrate with at least two distinct nucleic acid targets on one of itssurfaces, where the number of distinct nucleic acids can be considerablyhigher, typically being at least 10 nt, usually at least 20 nt and oftenat least 25 nt. A variety of different array formats have been developedand are known to those of skill in the art. The arrays of the subjectinvention find use in a variety of applications, including geneexpression analysis, drug screening, mutation analysis and the like, asdisclosed in the above-listed exemplary patent documents.

In addition to the above nucleic acid libraries, analogous libraries ofpolypeptides are also provided, where the polypeptides of the librarywill represent at least a portion of the polypeptides encoded by a genecorresponding to a sequence described herein.

Diagnostic and Other Methods Involving Detection of DifferentiallyExpressed Genes

The present invention provides methods of using the polynucleotidesdescribed herein in, for example, diagnosis of cancer and classificationof cancer cells according to expression profiles. In specificnon-limiting embodiments, the methods are useful for detecting cancercells, facilitating diagnosis of cancer and the severity of a cancer(e.g., tumor grade, tumor burden, and the like) in a subject,facilitating a determination of the prognosis of a subject, andassessing the responsiveness of the subject to therapy (e.g., byproviding a measure of therapeutic effect through, for example,assessing tumor burden during or following a chemotherapeutic regimen).Detection can be based on detection of a polynucleotide that isdifferentially expressed in a cancer cell, and/or detection of apolypeptide encoded by a polynucleotide that is differentially expressedin a cancer cell (“a polypeptide associated with cancer”). The detectionmethods of the invention can be conducted in vitro or in vivo, onisolated cells, or in whole tissues or a bodily fluid, e.g., blood,plasma, serum, urine, and the like).

In general, methods of the invention involving detection of a geneproduct (e.g., mRNA, cDNA generated from such mRNA, and polypeptides)involve contacting a sample with a probe specific for the gene productof interest. “Probe” as used herein in such methods is meant to refer toa molecule that specifically binds a gene product of interest (e.g., theprobe binds to the target gene product with a specificity sufficient todistinguish binding to target over non-specific binding to non-target(background) molecules). “Probes” include, but are not necessarilylimited to, nucleic acid probes (e.g., DNA, RNA, modified nucleic acid,and the like), antibodies (e.g., antibodies, antibody fragments thatretain binding to a target epitope, single chain antibodies, and thelike), or other polypeptide, peptide, or molecule (e.g., receptorligand) that specifically binds a target gene product of interest.

The probe and sample suspected of having the gene product of interestare contacted under conditions suitable for binding of the probe to thegene product. For example, contacting is generally for a time sufficientto allow binding of the probe to the gene product (e.g., from severalminutes to a few hours), and at a temperature and conditions ofosmolarity and the like that provide for binding of the probe to thegene product at a level that is sufficiently distinguishable frombackground binding of the probe (e.g., under conditions that minimizenon-specific binding). Suitable conditions for probe-target gene productbinding can be readily determined using controls and other techniquesavailable and known to one of ordinary skill in the art.

In this embodiment, the probe can be an antibody or other polypeptide,peptide, or molecule (e.g., receptor ligand) that specifically binds atarget polypeptide of interest.

The detection methods can be provided as part of a kit. Thus, theinvention further provides kits for detecting the presence and/or alevel of a polynucleotide that is differentially expressed in a cancercell (e.g., by detection of an mRNA encoded by the differentiallyexpressed gene of interest), and/or a polypeptide encoded thereby, in abiological sample. Procedures using these kits can be performed byclinical laboratories, experimental laboratories, medical practitioners,or private individuals. The kits of the invention for detecting apolypeptide encoded by a polynucleotide that is differentially expressedin a cancer cell comprise a moiety that specifically binds thepolypeptide, which may be a specific antibody. The kits of the inventionfor detecting a polynucleotide that is differentially expressed in acancer cell comprise a moiety that specifically hybridizes to such apolynucleotide. The kit may optionally provide additional componentsthat are useful in the procedure, including, but not limited to,buffers, developing reagents, labels, reacting surfaces, means fordetection, control samples, standards, instructions, and interpretiveinformation.

Detecting a Polypeptide Encoded by a Polynucleotide that isDifferentially Expressed in a Cancer Cell

In some embodiments, methods are provided for a detecting cancer cell bydetecting in a cell, a polypeptide encoded by a gene differentiallyexpressed in a cancer cell. Any of a variety of known methods can beused for detection, including, but not limited to, immunoassay, using anantibody specific for the encoded polypeptide, e.g., by enzyme-linkedimmunosorbent assay (ELISA), radioimmunoassay (RIA), and the like; andfunctional assays for the encoded polypeptide, e.g., binding activity orenzymatic activity.

For example, an immunofluorescence assay can be easily performed oncells without first isolating the encoded polypeptide. The cells arefirst fixed onto a solid support, such as a microscope slide ormicrotiter well. This fixing step can permeabilize the cell membrane.The permeablization of the cell membrane permits thepolypeptide-specific probe (e.g, antibody) to bind. Alternatively, wherethe polypeptide is secreted or membrane-bound, or is otherwiseaccessible at the cell-surface (e.g., receptors, and other moleculestably-associated with the outer cell membrane or otherwise stablyassociated with the cell membrane, such permeabilization may not benecessary.

Next, the fixed cells are exposed to an antibody specific for theencoded polypeptide. To increase the sensitivity of the assay, the fixedcells may be further exposed to a second antibody, which is labeled andbinds to the first antibody, which is specific for the encodedpolypeptide. Typically, the secondary antibody is detectably labeled,e.g., with a fluorescent marker. The cells which express the encodedpolypeptide will be fluorescently labeled and easily visualized underthe microscope. See, for example, Hashido et al. (1992) Biochem.Biophys. Res. Comm. 187:1241-1248.

As will be readily apparent to the ordinarily skilled artisan uponreading the present specification, the detection methods and othermethods described herein can be varied. Such variations are within theintended scope of the invention. For example, in the above detectionscheme, the probe for use in detection can be immobilized on a solidsupport, and the test sample contacted with the immobilized probe.Binding of the test sample to the probe can then be detected in avariety of ways, e.g., by detecting a detectable label bound to the testsample.

The present invention further provides methods for detecting thepresence of and/or measuring a level of a polypeptide in a biologicalsample, which polypeptide is encoded by a polynucleotide that representsa gene differentially expressed in cancer, particularly in apolynucleotide that represents a gene differentially cancer cell, usinga probe specific for the encoded polypeptide. In this embodiment, theprobe can be a an antibody or other polypeptide, peptide, or molecule(e.g., receptor ligand) that specifically binds a target polypeptide ofinterest.

The methods generally comprise: a) contacting the sample with anantibody specific for a differentially expressed polypeptide in a testcell; and b) detecting binding between the antibody and molecules of thesample. The level of antibody binding (either qualitative orquantitative) indicates the cancerous state of the cell. For example,where the differentially expressed gene is increased in cancerous cells,detection of an increased level of antibody binding to the test samplerelative to antibody binding level associated with a normal cellindicates that the test cell is cancerous.

Suitable controls include a sample known not to contain the encodedpolypeptide; and a sample contacted with an antibody not specific forthe encoded polypeptide, e.g., an anti-idiotype antibody. A variety ofmethods to detect specific antibody-antigen interactions are known inthe art and can be used in the method, including, but not limited to,standard immunohistological methods, immunoprecipitation, an enzymeimmunoassay, and a radioimmunoas say.

In general, the specific antibody will be detectably labeled, eitherdirectly or indirectly. Direct labels include radioisotopes; enzymeswhose products are detectable (e.g., luciferase, β-galactosidase, andthe like); fluorescent labels (e.g., fluorescein isothiocyanate,rhodamine, phycoerythrin, and the like); fluorescence emitting metals,e.g., ¹⁵²Eu, or others of the lanthanide series, attached to theantibody through metal chelating groups such as EDTA; chemiluminescentcompounds, e.g., luminol, isoluminol, acridinium salts, and the like;bioluminescent compounds, e.g., luciferin, aequorin (green fluorescentprotein), and the like.

The antibody may be attached (coupled) to an insoluble support, such asa polystyrene plate or a bead. Indirect labels include second antibodiesspecific for antibodies specific for the encoded polypeptide (“firstspecific antibody”), wherein the second antibody is labeled as describedabove; and members of specific binding pairs, e.g., biotin-avidin, andthe like. The biological sample may be brought into contact with andimmobilized on a solid support or carrier, such as nitrocellulose, thatis capable of immobilizing cells, cell particles, or soluble proteins.The support may then be washed with suitable buffers, followed bycontacting with a detectably-labeled first specific antibody. Detectionmethods are known in the art and will be chosen as appropriate to thesignal emitted by the detectable label. Detection is generallyaccomplished in comparison to suitable controls, and to appropriatestandards.

In some embodiments, the methods are adapted for use in vivo, e.g., tolocate or identify sites where cancer cells are present. In theseembodiments, a detectably-labeled moiety, e.g., an antibody, which isspecific for a cancer-associated polypeptide is administered to anindividual (e.g., by injection), and labeled cells are located usingstandard imaging techniques, including, but not limited to, magneticresonance imaging, computed tomography scanning, and the like. In thismanner, cancer cells are differentially labeled.

Detecting a Polynucleotide that Represents a Gene DifferentiallyExpressed in a Cancer Cell

In some embodiments, methods are provided for detecting a cancer cell bydetecting expression in the cell of a transcript or that isdifferentially expressed in a cancer cell. Any of a variety of knownmethods can be used for detection, including, but not limited to,detection of a transcript by hybridization with a polynucleotide thathybridizes to a polynucleotide that is differentially expressed in acancer cell; detection of a transcript by a polymerase chain reactionusing specific oligonucleotide primers; in situ hybridization of a cellusing as a probe a polynucleotide that hybridizes to a gene that isdifferentially expressed in a cancer cell and the like.

In many embodiments, the levels of a subject gene product are measured.By measured is meant qualitatively or quantitatively estimating thelevel of the gene product in a first biological sample either directly(e.g. by determining or estimating absolute levels of gene product) orrelatively by comparing the levels to a second control biologicalsample. In many embodiments the second control biological sample isobtained from an individual not having not having cancer. As will beappreciated in the art, once a standard control level of gene expressionis known, it can be used repeatedly as a standard for comparison. Othercontrol samples include samples of cancerous tissue.

The methods can be used to detect and/or measure mRNA levels of a genethat is differentially expressed in a cancer cell. In some embodiments,the methods comprise: a) contacting a sample with a polynucleotide thatcorresponds to a differentially expressed gene described herein underconditions that allow hybridization; and b) detecting hybridization, ifany. Detection of differential hybridization, when compared to asuitable control, is an indication of the presence in the sample of apolynucleotide that is differentially expressed in a cancer cell.Appropriate controls include, for example, a sample that is known not tocontain a polynucleotide that is differentially expressed in a cancercell. Conditions that allow hybridization are known in the art, and havebeen described in more detail above.

Detection can also be accomplished by any known method, including, butnot limited to, in situ hybridization, PCR (polymerase chain reaction),RT-PCR (reverse transcription-PCR), and “Northern” or RNA blotting,arrays, microarrays, etc, or combinations of such techniques, using asuitably labeled polynucleotide. A variety of labels and labelingmethods for polynucleotides are known in the art and can be used in theassay methods of the invention. Specific hybridization can be determinedby comparison to appropriate controls.

Polynucleotides described herein are used for a variety of purposes,such as probes for detection of and/or measurement of, transcriptionlevels of a polynucleotide that is differentially expressed in a cancercell. Additional disclosure about preferred regions of the disclosedpolynucleotide sequences is found in the Examples. A probe thathybridizes specifically to a polynucleotide disclosed herein shouldprovide a detection signal at least 2-, 5-, 10-, or 20-fold higher thanthe background hybridization provided with other unrelated sequences. Itshould be noted that “probe” as used in this context of detection ofnucleic acid is meant to refer to a polynucleotide sequence used todetect a differentially expressed gene product in a test sample. As willbe readily appreciated by the ordinarily skilled artisan, the probe canbe detectably labeled and contacted with, for example, an arraycomprising immobilized polynucleotides obtained from a test sample(e.g., mRNA). Alternatively, the probe can be immobilized on an arrayand the test sample detectably labeled. These and other variations ofthe methods of the invention are well within the skill in the art andare within the scope of the invention.

Labeled nucleic acid probes may be used to detect expression of a genecorresponding to the provided polynucleotide. In Northern blots, mRNA isseparated electrophoretically and contacted with a probe. A probe isdetected as hybridizing to an mRNA species of a particular size. Theamount of hybridization can be quantitated to determine relative amountsof expression, for example under a particular condition. Probes are usedfor in situ hybridization to cells to detect expression. Probes can alsobe used in vivo for diagnostic detection of hybridizing sequences.Probes are typically labeled with a radioactive isotope. Other types ofdetectable labels can be used such as chromophores, fluorophores, andenzymes. Other examples of nucleotide hybridization assays are describedin WO92/02526 and U.S. Pat. No. 5,124,246.

PCR is another means for detecting small amounts of target nucleicacids, methods for which may be found in Sambrook, et al. MolecularCloning: A Laboratory Manual, CSH Press 1989, pp. 14.2-14.33.

A detectable label may be included in the amplification reaction.Suitable detectable labels include fluorochromes, (e.g. fluoresceinisothiocyanate (FITC), rhodamine, Texas Red, phycoerythrin,allophycocyanin, 6-carboxyfluorescein (6-FAM),2′,7′-dimethoxy-4′,5′-dichloro-6-carboxyfluorescein,6-carboxy-X-rhodamine (ROX),6-carboxy-2′,4′,7′,4,7-hexachlorofluorescein (HEX), 5-carboxyfluorescein(5-FAM) or N,N,N′,N′-tetramethyl-6-carboxyrhodamine (TAMRA)),radioactive labels, (e.g. ³²P, ³⁵S, ³H, etc.), and the like. The labelmay be a two stage system, where the polynucleotides is conjugated tobiotin, haptens, etc. having a high affinity binding partner, e.g.avidin, specific antibodies, etc., where the binding partner isconjugated to a detectable label. The label may be conjugated to one orboth of the primers. Alternatively, the pool of nucleotides used in theamplification is labeled, so as to incorporate the label into theamplification product.

Arrays

Polynucleotide arrays provide a high throughput technique that can assaya large number of polynucleotides or polypeptides in a sample. Thistechnology can be used as a tool to test for differential expression.

A variety of methods of producing arrays, as well as variations of thesemethods, are known in the art and contemplated for use in the invention.For example, arrays can be created by spotting polynucleotide probesonto a substrate (e.g., glass, nitrocellulose, etc.) in atwo-dimensional matrix or array having bound probes. The probes can bebound to the substrate by either covalent bonds or by non-specificinteractions, such as hydrophobic interactions.

Samples of polynucleotides can be detectably labeled (e.g., usingradioactive or fluorescent labels) and then hybridized to the probes.Double stranded polynucleotides, comprising the labeled samplepolynucleotides bound to probe polynucleotides, can be detected once theunbound portion of the sample is washed away. Alternatively, thepolynucleotides of the test sample can be immobilized on the array, andthe probes detectably labeled. Techniques for constructing arrays andmethods of using these arrays are described in, for example, Schena etal. (1996) Proc Natl Acad Sci USA. 93(20):10614-9; Schena et al. (1995)Science 270(5235):467-70; Shalon et al. (1996) Genome Res. 6(7):639-45,U.S. Pat. No. 5,807,522, EP 799 897; WO 97/29212; WO 97/27317; EP 785280; WO 97/02357; U.S. Pat. No. 5,593,839; U.S. Pat. No. 5,578,832; EP728 520; U.S. Pat. No. 5,599,695; EP 721 016; U.S. Pat. No. 5,556,752;WO 95/22058; and U.S. Pat. No. 5,631,734. In most embodiments, the“probe” is detectably labeled. In other embodiments, the probe isimmobilized on the array and not detectably labeled.

Arrays can be used, for example, to examine differential expression ofgenes and can be used to determine gene function. For example, arrayscan be used to detect differential expression of a gene corresponding toa polynucleotide described herein, where expression is compared betweena test cell and control cell (e.g., cancer cells and normal cells). Forexample, high expression of a particular message in a cancer cell, whichis not observed in a corresponding normal cell, can indicate a cancerspecific gene product. Exemplary uses of arrays are further describedin, for example, Pappalarado et al., Sem. Radiation Oncol. (1998) 8:217;and Ramsay, Nature Biotechnol. (1998) 16:40. Furthermore, manyvariations on methods of detection using arrays are well within theskill in the art and within the scope of the present invention. Forexample, rather than immobilizing the probe to a solid support, the testsample can be immobilized on a solid support which is then contactedwith the probe.

Diagnosis, Prognosis, Assessment of Therapy (Therametrics), andManagement of Cancer

The polynucleotides described herein, as well as their gene products andcorresponding genes and gene products, are of particular interest asgenetic or biochemical markers (e.g., in blood or tissues) that willdetect the earliest changes along the carcinogenesis pathway and/or tomonitor the efficacy of various therapies and preventive interventions.

For example, the level of expression of certain polynucleotides can beindicative of a poorer prognosis, and therefore warrant more aggressivechemo- or radio-therapy for a patient or vice versa. The correlation ofnovel surrogate tumor specific features with response to treatment andoutcome in patients can define prognostic indicators that allow thedesign of tailored therapy based on the molecular profile of the tumor.These therapies include antibody targeting, antagonists (e.g., smallmolecules), and gene therapy.

Determining expression of certain polynucleotides and comparison of apatient's profile with known expression in normal tissue and variants ofthe disease allows a determination of the best possible treatment for apatient, both in terms of specificity of treatment and in terms ofcomfort level of the patient. Surrogate tumor markers, such aspolynucleotide expression, can also be used to better classify, and thusdiagnose and treat, different forms and disease states of cancer. Twoclassifications widely used in oncology that can benefit fromidentification of the expression levels of the genes corresponding tothe polynucleotides described herein are staging of the cancerousdisorder, and grading the nature of the cancerous tissue.

The polynucleotides that correspond to differentially expressed genes,as well as their encoded gene products, can be useful to monitorpatients having or susceptible to cancer to detect potentially malignantevents at a molecular level before they are detectable at a grossmorphological level. In addition, the polynucleotides described herein,as well as the genes corresponding to such polynucleotides, can beuseful as therametrics, e.g., to assess the effectiveness of therapy byusing the polynucleotides or their encoded gene products, to assess, forexample, tumor burden in the patient before, during, and after therapy.

Furthermore, a polynucleotide identified as corresponding to a gene thatis differentially expressed in, and thus is important for, one type ofcancer can also have implications for development or risk of developmentof other types of cancer, e.g., where a polynucleotide represents a genedifferentially expressed across various cancer types. Thus, for example,expression of a polynucleotide corresponding to a gene that has clinicalimplications for cancer can also have clinical implications formetastatic breast cancer, colon cancer, or ovarian cancer, etc.

Staging. Staging is a process used by physicians to describe howadvanced the cancerous state is in a patient. Staging assists thephysician in determining a prognosis, planning treatment and evaluatingthe results of such treatment. Staging systems vary with the types ofcancer, but generally involve the following “TNM” system: the type oftumor, indicated by T; whether the cancer has metastasized to nearbylymph nodes, indicated by N; and whether the cancer has metastasized tomore distant parts of the body, indicated by M. Generally, if a canceris only detectable in the area of the primary lesion without havingspread to any lymph nodes it is called Stage I. If it has spread only tothe closest lymph nodes, it is called Stage II. In Stage III, the cancerhas generally spread to the lymph nodes in near proximity to the site ofthe primary lesion. Cancers that have spread to a distant part of thebody, such as the liver, bone, brain or other site, are Stage IV, themost advanced stage.

The polynucleotides and corresponding genes and gene products describedherein can facilitate fine-tuning of the staging process by identifyingmarkers for the aggressiveness of a cancer, e.g. the metastaticpotential, as well as the presence in different areas of the body. Thus,a Stage II cancer with a polynucleotide signifying a high metastaticpotential cancer can be used to change a borderline Stage II tumor to aStage III tumor, justifying more aggressive therapy. Conversely, thepresence of a polynucleotide signifying a lower metastatic potentialallows more conservative staging of a tumor.

One type of breast cancer is ductal carcinoma in situ (DCIS): DCIS iswhen the breast cancer cells are completely contained within the breastducts (the channels in the breast that carry milk to the nipple), andhave not spread into the surrounding breast tissue. This may also bereferred to as non-invasive or intraductal cancer, as the cancer cellshave not yet spread into the surrounding breast tissue and so usuallyhave not spread into any other part of the body.

Lobular carcinoma in situ breast cancer (LCIS) means that cell changesare found in the lining of the lobules of the breast. It can be presentin both breasts. It is also referred to as non-invasive cancer as it hasnot spread into the surrounding breast tissue.

Invasive breast cancer can be staged as follows: Stage 1 tumours: thesemeasure less than two centimetres. The lymph glands in the armpit arenot affected and there are no signs that the cancer has spread elsewherein the body; Stage 2 tumours: these measure between two and fivecentimetres, or the lymph glands in the armpit are affected, or both.However, there are no signs that the cancer has spread further; Stage 3tumours: these are larger than five centimetres and may be attached tosurrounding structures such as the muscle or skin. The lymph glands areusually affected, but there are no signs that the cancer has spreadbeyond the breast or the lymph glands in the armpit; Stage 4 tumours:these are of any size, but the lymph glands are usually affected and thecancer has spread to other parts of the body. This is secondary breastcancer.

Grading of cancers. Grade is a term used to describe how closely a tumorresembles normal tissue of its same type. The microscopic appearance ofa tumor is used to identify tumor grade based on parameters such as cellmorphology, cellular organization, and other markers of differentiation.As a general rule, the grade of a tumor corresponds to its rate ofgrowth or aggressiveness, with undifferentiated or high-grade tumorsgenerally being more aggressive than well-differentiated or low-gradetumors.

The polynucleotides of the Sequence Listing, and their correspondinggenes and gene products, can be especially valuable in determining thegrade of the tumor, as they not only can aid in determining thedifferentiation status of the cells of a tumor, they can also identifyfactors other than differentiation that are valuable in determining theaggressiveness of a tumor, such as metastatic potential.

Low grade means that the cancer cells look very like the normal cells.They are usually slowly growing and are less likely to spread. In highgrade tumors the cells look very abnormal. They are likely to grow morequickly and are more likely to spread.

Assessment of proliferation of cells in tumor. The differentialexpression level of the polynucleotides described herein can facilitateassessment of the rate of proliferation of tumor cells, and thus providean indicator of the aggressiveness of the rate of tumor growth. Forexample, assessment of the relative expression levels of genes involvedin cell cycle can provide an indication of cellular proliferation, andthus serve as a marker of proliferation.

Detection of Cancer.

The polynucleotides corresponding to genes that exhibit the appropriateexpression pattern can be used to detect cancer in a subject. Theexpression of appropriate polynucleotides can be used in the diagnosis,prognosis and management of cancer. Detection of cancer can bedetermined using expression levels of any of these sequences alone or incombination with the levels of expression of other known cancer genes.Determination of the aggressive nature and/or the metastatic potentialof a cancer can be determined by comparing levels of one or more geneproducts of the genes corresponding to the polynucleotides describedherein, and comparing total levels of another sequence known to vary incancerous tissue, e.g., expression of p53, DCC, ras, FAP (see, e.g.,Fearon E R, et al., Cell (1990) 61(5):759; Hamilton S R et al., Cancer(1993) 72:957; Bodmer W, et al., Nat. Genet. (1994) 4(3):217; Fearon ER, Ann N Y Acad. Sci. (1995) 768:101). For example, development ofcancer can be detected by examining the level of expression of a genecorresponding to a polynucleotides described herein to the levels ofoncogenes (e.g. ras) or tumor suppressor genes (e.g. FAP or p53). Thusexpression of specific marker polynucleotides can be used todiscriminate between normal and cancerous tissue, to discriminatebetween cancers with different cells of origin, to discriminate betweencancers with different potential metastatic rates, etc. For a review ofother markers of cancer, see, e.g., Hanahan et al. (2000) Cell100:57-70.

Treatment of Cancer

The invention further provides methods for reducing growth of cancercells. The methods provide for decreasing the expression of a gene thatis differentially expressed in a cancer cell or decreasing the level ofand/or decreasing an activity of a cancer-associated polypeptide. Ingeneral, the methods comprise contacting a cancer cell with a substancethat modulates (1) expression of a gene that is differentially expressedin cancer; or (2) a level of and/or an activity of a cancer-associatedpolypeptide.

“Reducing growth of cancer cells” includes, but is not limited to,reducing proliferation of cancer cells, and reducing the incidence of anon-cancerous cell becoming a cancerous cell. Whether a reduction incancer cell growth has been achieved can be readily determined using anyknown assay, including, but not limited to, [³H]-thymidineincorporation; counting cell number over a period of time; detectingand/or measuring a marker associated with breast cancer (e.g., PSA).

The present invention provides methods for treating cancer, generallycomprising administering to an individual in need thereof a substancethat reduces cancer cell growth, in an amount sufficient to reducecancer cell growth and treat the cancer. Whether a substance, or aspecific amount of the substance, is effective in treating cancer can beassessed using any of a variety of known diagnostic assays for cancer,including, but not limited to, proctoscopy, rectal examination, biopsy,contrast radiographic studies, CAT scan, and detection of a tumor markerassociated with cancer in the blood of the individual (e.g., PSA(breast-specific antigen)). The substance can be administeredsystemically or locally. Thus, in some embodiments, the substance isadministered locally, and cancer growth is decreased at the site ofadministration. Local administration may be useful in treating, e.g., asolid tumor.

A substance that reduces cancer cell growth can be targeted to a cancercell. Thus, in some embodiments, the invention provides a method ofdelivering a drug to a cancer cell, comprising administering adrug-antibody complex to a subject, wherein the antibody is specific fora cancer-associated polypeptide, and the drug is one that reduces cancercell growth, a variety of which are known in the art. Targeting can beaccomplished by coupling (e.g., linking, directly or via a linkermolecule, either covalently or non-covalently, so as to form adrug-antibody complex) a drug to an antibody specific for acancer-associated polypeptide. Methods of coupling a drug to an antibodyare well known in the art and need not be elaborated upon herein.

Tumor Classification and Patient Stratification

The invention further provides for methods of classifying tumors, andthus grouping or “stratifying” patients, according to the expressionprofile of selected differentially expressed genes in a tumor.Differentially expressed genes can be analyzed for correlation withother differentially expressed genes in a single tumor type or acrosstumor types. Genes that demonstrate consistent correlation in expressionprofile in a given cancer cell type (e.g., in a cancer cell or type ofcancer) can be grouped together, e.g., when one gene is overexpressed ina tumor, a second gene is also usually overexpressed. Tumors can then beclassified according to the expression profile of one or more genesselected from one or more groups.

The tumor of each patient in a pool of potential patients can beclassified as described above. Patients having similarly classifiedtumors can then be selected for participation in an investigative orclinical trial of a cancer therapeutic where a homogeneous population isdesired. The tumor classification of a patient can also be used inassessing the efficacy of a cancer therapeutic in a heterogeneouspatient population. In addition, therapy for a patient having a tumor ofa given expression profile can then be selected accordingly.

In another embodiment, differentially expressed gene products (e.g.,polypeptides or polynucleotides encoding such polypeptides) may beeffectively used in treatment through vaccination. The growth of cancercells is naturally limited in part due to immune surveillance.Stimulation of the immune system using a particular tumor-specificantigen enhances the effect towards the tumor expressing the antigen. Anactive vaccine comprising a polypeptide encoded by the cDNA of thisinvention would be appropriately administered to subjects having analteration, e.g., overabundance, of the corresponding RNA, or thosepredisposed for developing cancer cells with an alteration of the sameRNA. Polypeptide antigens are typically combined with an adjuvant aspart of a vaccine composition. The vaccine is preferably administeredfirst as a priming dose, and then again as a boosting dose, usually atleast four weeks later. Further boosting doses may be given to enhancethe effect. The dose and its timing are usually determined by the personresponsible for the treatment.

The invention also encompasses the selection of a therapeutic regimenbased upon the expression profile of differentially expressed genes inthe patient's tumor. For example, a tumor can be analyzed for itsexpression profile of the genes corresponding to SEQ ID NOS: 1-13996 asdescribed herein, e.g., the tumor is analyzed to determine which genesare expressed at elevated levels or at decreased levels relative tonormal cells of the same tissue type. The expression patterns of thetumor are then compared to the expression patterns of tumors thatrespond to a selected therapy. Where the expression profiles of the testtumor cell and the expression profile of a tumor cell of known drugresponsivity at least substantially match (e.g., selected sets of genesat elevated levels in the tumor of known drug responsivity and are alsoat elevated levels in the test tumor cell), then the therapeutic agentselected for therapy is the drug to which tumors with that expressionpattern respond.

Pattern Matching in Diagnosis Using Arrays

In another embodiment, the diagnostic and/or prognostic methods of theinvention involve detection of expression of a selected set of genes ina test sample to produce a test expression pattern (TEP). The TEP iscompared to a reference expression pattern (REP), which is generated bydetection of expression of the selected set of genes in a referencesample (e.g., a positive or negative control sample). The selected setof genes includes at least one of the genes of the invention, whichgenes correspond to the polynucleotide sequences described herein. Ofparticular interest is a selected set of genes that includes genedifferentially expressed in the disease for which the test sample is tobe screened.

Identification of Therapeutic Targets and Anti-Cancer Therapeutic Agents

The present invention also encompasses methods for identification ofagents having the ability to modulate activity of a differentiallyexpressed gene product, as well as methods for identifying adifferentially expressed gene product as a therapeutic target fortreatment of cancer.

Identification of compounds that modulate activity of a differentiallyexpressed gene product can be accomplished using any of a variety ofdrug screening techniques. Such agents are candidates for development ofcancer therapies. Of particular interest are screening assays for agentsthat have tolerable toxicity for normal, non-cancerous human cells. Thescreening assays of the invention are generally based upon the abilityof the agent to modulate an activity of a differentially expressed geneproduct and/or to inhibit or suppress phenomenon associated with cancer(e.g., cell proliferation, colony formation, cell cycle arrest,metastasis, and the like).

Screening of Candidate Agents

Screening assays can be based upon any of a variety of techniquesreadily available and known to one of ordinary skill in the art. Ingeneral, the screening assays involve contacting a cancerous cell with acandidate agent, and assessing the effect upon biological activity of adifferentially expressed gene product. The effect upon a biologicalactivity can be detected by, for example, detection of expression of agene product of a differentially expressed gene (e.g., a decrease inmRNA or polypeptide levels, would in turn cause a decrease in biologicalactivity of the gene product). Alternatively or in addition, the effectof the candidate agent can be assessed by examining the effect of thecandidate agent in a functional assay. For example, where thedifferentially expressed gene product is an enzyme, then the effect uponbiological activity can be assessed by detecting a level of enzymaticactivity associated with the differentially expressed gene product. Thefunctional assay will be selected according to the differentiallyexpressed gene product. In general, where the differentially expressedgene is increased in expression in a cancerous cell, agents of interestare those that decrease activity of the differentially expressed geneproduct.

Assays described infra can be readily adapted in the screening assayembodiments of the invention. Exemplary assays useful in screeningcandidate agents include, but are not limited to, hybridization-basedassays (e.g., use of nucleic acid probes or primers to assess expressionlevels), antibody-based assays (e.g., to assess levels of polypeptidegene products), binding assays (e.g., to detect interaction of acandidate agent with a differentially expressed polypeptide, whichassays may be competitive assays where a natural or synthetic ligand forthe polypeptide is available), and the like. Additional exemplary assaysinclude, but are not necessarily limited to, cell proliferation assays,antisense knockout assays, assays to detect inhibition of cell cycle,assays of induction of cell death/apoptosis, and the like. Generallysuch assays are conducted in vitro, but many assays can be adapted forin vivo analyses, e.g., in an animal model of the cancer.

Identification of Therapeutic Targets

In another embodiment, the invention contemplates identification ofdifferentially expressed genes and gene products as therapeutic targets.In some respects, this is the converse of the assays described above foridentification of agents having activity in modulating (e.g., decreasingor increasing) activity of a differentially expressed gene product.

In this embodiment, therapeutic targets are identified by examining theeffect(s) of an agent that can be demonstrated or has been demonstratedto modulate a cancerous phenotype (e.g., inhibit or suppress or preventdevelopment of a cancerous phenotype). Such agents are generallyreferred to herein as an “anti-cancer agent”, which agents encompasschemotherapeutic agents. For example, the agent can be an antisenseoligonucleotide that is specific for a selected gene transcript. Forexample, the antisense oligonucleotide may have a sequence correspondingto a sequence of a differentially expressed gene described herein, e.g.,a sequence of one of SEQ ID NOS: 1-13996.

Assays for identification of therapeutic targets can be conducted in avariety of ways using methods that are well known to one of ordinaryskill in the art. For example, a test cancerous cell that expresses oroverexpresses a differentially expressed gene is contacted with ananti-cancer agent, the effect upon a cancerous phenotype and abiological activity of the candidate gene product assessed. Thebiological activity of the candidate gene product can be assayed beexamining, for example, modulation of expression of a gene encoding thecandidate gene product (e.g., as detected by, for example, an increaseor decrease in transcript levels or polypeptide levels), or modulationof an enzymatic or other activity of the gene product. The cancerousphenotype can be, for example, cellular proliferation, loss of contactinhibition of growth (e.g., colony formation), tumor growth (in vitro orin vivo), and the like. Alternatively or in addition, the effect ofmodulation of a biological activity of the candidate target gene uponcell death/apoptosis or cell cycle regulation can be assessed.

Inhibition or suppression of a cancerous phenotype, or an increase incell death or apoptosis as a result of modulation of biological activityof a candidate gene product indicates that the candidate gene product isa suitable target for cancer therapy. Assays described infra can bereadily adapted for assays for identification of therapeutic targets.Generally such assays are conducted in vitro, but many assays can beadapted for in vivo analyses, e.g., in an appropriate, art-acceptedanimal model of the cancer.

Candidate Agents

The term “agent” as used herein describes any molecule, e.g. protein orpharmaceutical, with the capability of modulating a biological activityof a gene product of a differentially expressed gene. Generally aplurality of assay mixtures are run in parallel with different agentconcentrations to obtain a differential response to the variousconcentrations. Typically, one of these concentrations serves as anegative control, i.e. at zero concentration or below the level ofdetection.

Candidate agents encompass numerous chemical classes, though typicallythey are organic molecules, preferably small organic compounds having amolecular weight of more than 50 and less than about 2,500 daltons.Candidate agents comprise functional groups necessary for structuralinteraction with proteins, particularly hydrogen bonding, and typicallyinclude at least an amine, carbonyl, hydroxyl or carboxyl group,preferably at least two of the functional chemical groups. The candidateagents often comprise cyclical carbon or heterocyclic structures and/oraromatic or polyaromatic structures substituted with one or more of theabove functional groups. Candidate agents are also found amongbiomolecules including, but not limited to: peptides, saccharides, fattyacids, steroids, purines, pyrimidines, derivatives, structural analogsor combinations thereof.

Candidate agents are obtained from a wide variety of sources includinglibraries of synthetic or natural compounds. For example, numerous meansare available for random and directed synthesis of a wide variety oforganic compounds and biomolecules, including expression of randomizedoligonucleotides and oligopeptides. Alternatively, libraries of naturalcompounds in the form of bacterial, fungal, plant and animal extracts(including extracts from human tissue to identify endogenous factorsaffecting differentially expressed gene products) are available orreadily produced. Additionally, natural or synthetically producedlibraries and compounds are readily modified through conventionalchemical, physical and biochemical means, and may be used to producecombinatorial libraries. Known pharmacological agents may be subjectedto directed or random chemical modifications, such as acylation,alkylation, esterification, amidification, etc. to produce structuralanalogs.

Exemplary candidate agents of particular interest include, but are notlimited to, antisense and RNAi polynucleotides, and antibodies, solublereceptors, and the like. Antibodies and soluble receptors are ofparticular interest as candidate agents where the target differentiallyexpressed gene product is secreted or accessible at the cell-surface(e.g., receptors and other molecule stably-associated with the outercell membrane).

For method that involve RNAi (RNA interference), a double stranded RNA(dsRNA) molecule is usually used. The dsRNA is prepared to besubstantially identical to at least a segment of a subjectpolynucleotide (e.g. a cDNA or gene). In general, the dsRNA is selectedto have at least 70%, 75%, 80%, 85% or 90% sequence identity with thesubject polynucleotide over at least a segment of the candidate gene. Inother instances, the sequence identity is even higher, such as 95%, 97%or 99%, and in still other instances, there is 100% sequence identitywith the subject polynucleotide over at least a segment of the subjectpolynucleotide. The size of the segment over which there is sequenceidentity can vary depending upon the size of the subject polynucleotide.In general, however, there is substantial sequence identity over atleast 15, 20, 25, 30, 35, 40 or 50 nucleotides. In other instances,there is substantial sequence identity over at least 100, 200, 300, 400,500 or 1000 nucleotides; in still other instances, there is substantialsequence identity over the entire length of the subject polynucleotide,i.e., the coding and non-coding region of the candidate gene.

Because only substantial sequence similarity between the subjectpolynucleotide and the dsRNA is necessary, sequence variations betweenthese two species arising from genetic mutations, evolutionarydivergence and polymorphisms can be tolerated. Moreover, as describedfurther infra, the dsRNA can include various modified or nucleotideanalogs.

Usually the dsRNA consists of two separate complementary RNA strands.However, in some instances, the dsRNA may be formed by a single strandof RNA that is self-complementary, such that the strand loops back uponitself to form a hairpin loop. Regardless of form, RNA duplex formationcan occur inside or outside of a cell.

The size of the dsRNA that is utilized varies according to the size ofthe subject polynucleotide whose expression is to be suppressed and issufficiently long to be effective in reducing expression of the subjectpolynucleotide in a cell. Generally, the dsRNA is at least 10-15nucleotides long. In certain applications, the dsRNA is less than 20,21, 22, 23, 24 or 25 nucleotides in length. In other instances, thedsRNA is at least 50, 100, 150 or 200 nucleotides in length. The dsRNAcan be longer still in certain other applications, such as at least 300,400, 500 or 600 nucleotides. Typically, the dsRNA is not longer than3000 nucleotides. The optimal size for any particular subjectpolynucleotide can be determined by one of ordinary skill in the artwithout undue experimentation by varying the size of the dsRNA in asystematic fashion and determining whether the size selected iseffective in interfering with expression of the subject polynucleotide.

dsRNA can be prepared according to any of a number of methods that areknown in the art, including in vitro and in vivo methods, as well as bysynthetic chemistry approaches.

In vitro methods. Certain methods generally involve inserting thesegment corresponding to the candidate gene that is to be transcribedbetween a promoter or pair of promoters that are oriented to drivetranscription of the inserted segment and then utilizing an appropriateRNA polymerase to carry out transcription. One such arrangement involvespositioning a DNA fragment corresponding to the candidate gene orsegment thereof into a vector such that it is flanked by two opposablepolymerase-specific promoters that can be same or different.Transcription from such promoters produces two complementary RNA strandsthat can subsequently anneal to form the desired dsRNA. Exemplaryplasmids for use in such systems include the plasmid (PCR 4.0 TOPO)(available from Invitrogen). Another example is the vector pGEM-T(Promega, Madison, Wis.) in which the oppositely oriented promoters areT7 and SP6; the T3 promoter can also be utilized.

In a second arrangement, DNA fragments corresponding to the segment ofthe subject polynucleotide that is to be transcribed is inserted both inthe sense and antisense orientation downstream of a single promoter. Inthis system, the sense and antisense fragments are cotranscribed togenerate a single RNA strand that is self-complementary and thus canform dsRNA.

Various other in vitro methods have been described. Examples of suchmethods include, but are not limited to, the methods described by Sadheret al. (Biochem. Int. 14:1015, 1987); by Bhattacharyya (Nature 343:484,1990); and by Livache, et al. (U.S. Pat. No. 5,795,715), each of whichis incorporated herein by reference in its entirety.

Single-stranded RNA can also be produced using a combination ofenzymatic and organic synthesis or by total organic synthesis. The useof synthetic chemical methods enable one to introduce desired modifiednucleotides or nucleotide analogs into the dsRNA.

In vivo methods. dsRNA can also be prepared in vivo according to anumber of established methods (see, e.g., Sambrook, et al. (1989)Molecular Cloning: A Laboratory Manual, 2^(nd) ed.; Transcription andTranslation (B. D. Hames, and S. J. Higgins, Eds., 1984); DNA Cloning,volumes I and II (D. N. Glover, Ed., 1985); and OligonucleotideSynthesis (M. J. Gait, Ed., 1984, each of which is incorporated hereinby reference in its entirety).

Once the single-stranded RNA has been formed, the complementary strandsare allowed to anneal to form duplex RNA. Transcripts are typicallytreated with DNAase and further purified according to establishedprotocols to remove proteins. Usually such purification methods are notconducted with phenol:chloroform. The resulting purified transcripts aresubsequently dissolved in RNAase free water or a buffer of suitablecomposition.

dsRNA is generated by annealing the sense and anti-sense RNA in vitro.Generally, the strands are initially denatured to keep the strandsseparate and to avoid self-annealing. During the annealing process,typically certain ratios of the sense and antisense strands are combinedto facilitate the annealing process. In some instances, a molar ratio ofsense to antisense strands of 3:7 is used; in other instances, a ratioof 4:6 is utilized; and in still other instances, the ratio is 1:1.

The buffer composition utilized during the annealing process can in someinstances affect the efficacy of the annealing process and subsequenttransfection procedure. While some have indicated that the bufferedsolution used to carry out the annealing process should include apotassium salt such as potassium chloride (e.g. at a concentration ofabout 80 mM). In some embodiments, the buffer is substantiallypostassium free. Once single-stranded RNA has annealed to form duplexRNA, typically any single-strand overhangs are removed using an enzymethat specifically cleaves such overhangs (e.g., RNAase A or RNAase T).

Once the dsRNA has been formed, it is introduced into a reference cell,which can include an individual cell or a population of cells (e.g., atissue, an embryo and an entire organism). The cell can be fromessentially any source, including animal, plant, viral, bacterial,fungal and other sources. If a tissue, the tissue can include dividingor nondividing and differentiated or undifferentiated cells. Further,the tissue can include germ line cells and somatic cells. Examples ofdifferentiated cells that can be utilized include, but are not limitedto, neurons, glial cells, blood cells, megakaryocytes, lymphocytes,macrophages, neutrophils, eosinophils, basophils, mast cells,leukocytes, granulocytes, keratinocytes, adipocytes, osteoblasts,osteoclasts, hepatocytes, cells of the endocrine or exocrine glands,fibroblasts, myocytes, cardiomyocytes, and endothelial cells. The cellcan be an individual cell of an embryo, and can be a blastocyte or anoocyte.

Certain methods are conducted using model systems for particularcellular states (e.g., a disease). For instance, certain methodsprovided herein are conducted with a cancer cell lines that serves as amodel system for investigating genes that are correlated with variouscancers.

A number of options can be utilized to deliver the dsRNA into a cell orpopulation of cells such as in a cell culture, tissue or embryo. Forinstance, RNA can be directly introduced intracellularly. Variousphysical methods are generally utilized in such instances, such asadministration by microinjection (see, e.g., Zernicka-Goetz, et al.(1997) Development 124:1133-1137; and Wianny, et al. (1998) Chromosoma107: 430-439).

Other options for cellular delivery include permeabilizing the cellmembrane and electroporation in the presence of the dsRNA,liposome-mediated transfection, or transfection using chemicals such ascalcium phosphate. A number of established gene therapy techniques canalso be utilized to introduce the dsRNA into a cell. By introducing aviral construct within a viral particle, for instance, one can achieveefficient introduction of an expression construct into the cell andtranscription of the RNA encoded by the construct.

If the dsRNA is to be introduced into an organism or tissue, gene guntechnology is an option that can be employed. This generally involvesimmobilizing the dsRNA on a gold particle which is subsequently firedinto the desired tissue. Research has also shown that mammalian cellshave transport mechanisms for taking in dsRNA (see, e.g., Asher, et al.(1969) Nature 223:715-717). Consequently, another delivery option is toadminister the dsRNA extracellularly into a body cavity, interstitialspace or into the blood system of the mammal for subsequent uptake bysuch transport processes. The blood and lymph systems and thecerebrospinal fluid are potential sites for injecting dsRNA. Oral,topical, parenteral, rectal and intraperitoneal administration are alsopossible modes of administration.

The composition introduced can also include various other agents inaddition to the dsRNA. Examples of such agents include, but are notlimited to, those that stabilize the dsRNA, enhance cellular uptakeand/or increase the extent of interference. Typically, the dsRNA isintroduced in a buffer that is compatible with the composition of thecell into which the RNA is introduced to prevent the cell from beingshocked. The minimum size of the dsRNA that effectively achieves genesilencing can also influence the choice of delivery system and solutioncomposition.

Sufficient dsRNA is introduced into the tissue to cause a detectablechange in expression of a target gene (assuming the candidate gene is infact being expressed in the cell into which the dsRNA is introduced)using available detection methodologies. Thus, in some instances,sufficient dsRNA is introduced to achieve at least a 5-10% reduction incandidate gene expression as compared to a cell in which the dsRNA isnot introduced. In other instances, inhibition is at least 20, 30, 40 or50%. In still other instances, the inhibition is at least 60, 70, 80, 90or 95%. Expression in some instances is essentially completely inhibitedto undetectable levels.

The amount of dsRNA introduced depends upon various factors such as themode of administration utilized, the size of the dsRNA, the number ofcells into which dsRNA is administered, and the age and size of ananimal if dsRNA is introduced into an animal.

An appropriate amount can be determined by those of ordinary skill inthe art by initially administering dsRNA at several differentconcentrations for example, for example. In certain instances when dsRNAis introduced into a cell culture, the amount of dsRNA introduced intothe cells varies from about 0.5 to 3 μg per 10⁶ cells.

A number of options are available to detect interference of candidategene expression (i.e., to detect candidate gene silencing). In general,inhibition in expression is detected by detecting a decrease in thelevel of the protein encoded by the candidate gene, determining thelevel of mRNA transcribed from the gene and/or detecting a change inphenotype associated with candidate gene expression.

Use of Polypeptides to Screen for Peptide Analogs and Antagonists

Polypeptides encoded by differentially expressed genes identified hereincan be used to screen peptide libraries to identify binding partners,such as receptors, from among the encoded polypeptides. Peptidelibraries can be synthesized according to methods known in the art (see,e.g., U.S. Pat. No. 5,010,175 and WO 91/17823).

Agonists or antagonists of the polypeptides of the invention can bescreened using any available method known in the art, such as signaltransduction, antibody binding, receptor binding, mitogenic assays,chemotaxis assays, etc. The assay conditions ideally should resemble theconditions under which the native activity is exhibited in vivo, thatis, under physiologic pH, temperature, and ionic strength. Suitableagonists or antagonists will exhibit strong inhibition or enhancement ofthe native activity at concentrations that do not cause toxic sideeffects in the subject. Agonists or antagonists that compete for bindingto the native polypeptide can require concentrations equal to or greaterthan the native concentration, while inhibitors capable of bindingirreversibly to the polypeptide can be added in concentrations on theorder of the native concentration.

Such screening and experimentation can lead to identification of apolypeptide binding partner, such as a receptor, encoded by a gene or acDNA corresponding to a polynucleotide described herein, and at leastone peptide agonist or antagonist of the binding partner. Such agonistsand antagonists can be used to modulate, enhance, or inhibit receptorfunction in cells to which the receptor is native, or in cells thatpossess the receptor as a result of genetic engineering. Further, if thereceptor shares biologically important characteristics with a knownreceptor, information about agonist/antagonist binding can facilitatedevelopment of improved agonists/antagonists of the known receptor.

Vaccines and Uses

The differentially expressed nucleic acids and polypeptides produced bythe nucleic acids of the invention can also be used to modulate primaryimmune response to prevent or treat cancer. Every immune response is acomplex and intricately regulated sequence of events involving severalcell types. It is triggered when an antigen enters the body andencounters a specialized class of cells called antigen-presenting cells(APCs). These APCs capture a minute amount of the antigen and display itin a form that can be recognized by antigen-specific helper Tlymphocytes. The helper (Th) cells become activated and, in turn,promote the activation of other classes of lymphocytes, such as B cellsor cytotoxic T cells. The activated lymphocytes then proliferate andcarry out their specific effector functions, which in many casessuccessfully activate or eliminate the antigen. Thus, activating theimmune response to a particular antigen associated with a cancer cellcan protect the patient from developing cancer or result in lymphocyteseliminating cancer cells expressing the antigen.

Gene products, including polypeptides, mRNA (particularly mRNAs havingdistinct secondary and/or tertiary structures), cDNA, or complete gene,can be prepared and used in vaccines for the treatment or prevention ofhyperproliferative disorders and cancers. The nucleic acids andpolypeptides can be utilized to enhance the immune response, preventtumor progression, prevent hyperproliferative cell growth, and the like.Methods for selecting nucleic acids and polypeptides that are capable ofenhancing the immune response are known in the art. Preferably, the geneproducts for use in a vaccine are gene products which are present on thesurface of a cell and are recognizable by lymphocytes and antibodies.

The gene products may be formulated with pharmaceutically acceptablecarriers into pharmaceutical compositions by methods known in the art.The composition is useful as a vaccine to prevent or treat cancer. Thecomposition may further comprise at least one co-immunostimulatorymolecule, including but not limited to one or more majorhistocompatibility complex (MHC) molecules, such as a class I or classII molecule, preferably a class 1 molecule. The composition may furthercomprise other stimulator molecules including B7.1, B7.2, ICAM-1,ICAM-2, LFA-1, LFA-3, CD72 and the like, immunostimulatorypolynucleotides (which comprise an 5′-CG-3′ wherein the cytosine isunmethylated), and cytokines which include but are not limited to IL-1through IL-15, TNF-α, IFN-γ, RANTES, G-CSF, M-CSF, IFN-α, CTAP III,ENA-78, GRO, I-309, PF-4, IP-10, LD-78, MGSA, MIP-1α, MIP-1β, orcombination thereof, and the like for immunopotentiation. In oneembodiment, the immunopotentiators of particular interest are those thatfacilitate a Th1 immune response.

The gene products may also be prepared with a carrier that will protectthe gene products against rapid elimination from the body, such as acontrolled release formulation, including implants and microencapsulateddelivery systems. Biodegradable polymers can be used, such as ethylenevinyl acetate, polyanhydrides, polyglycolic acid, collagen,polyorthoesters, polylactic acid, and the like. Methods for preparationof such formulations are known in the art.

In the methods of preventing or treating cancer, the gene products maybe administered via one of several routes including but not limited totransdermal, transmucosal, intravenous, intramuscular, subcutaneous,intradermal, intraperitoneal, intrathecal, intrapleural, intrauterine,rectal, vaginal, topical, intratumor, and the like. For transmucosal ortransdermal administration, penetrants appropriate to the barrier to bepermeated are used in the formulation. Such penetrants are generallyknown in the art, and include, for example, administration bile saltsand fusidic acid derivatives. In addition, detergents may be used tofacilitate permeation. Transmucosal administration may be by nasalsprays or suppositories. For oral administration, the gene products areformulated into conventional oral administration form such as capsules,tablets, elixirs and the like.

The gene product is administered to a patient in an amount effective toprevent or treat cancer. In general, it is desirable to provide thepatient with a dosage of gene product of at least about 1 pg per Kg bodyweight, preferably at least about 1 ng per Kg body weight, morepreferably at least about 1 μg or greater per Kg body weight of therecipient. A range of from about 1 ng per Kg body weight to about 100 mgper Kg body weight is preferred although a lower or higher dose may beadministered. The dose is effective to prime, stimulate and/or cause theclonal expansion of antigen-specific T lymphocytes, preferably cytotoxicT lymphocytes, which in turn are capable of preventing or treatingcancer in the recipient. The dose is administered at least once and maybe provided as a bolus or a continuous administration. Multipleadministrations of the dose over a period of several weeks to months maybe preferable. Subsequent doses may be administered as indicated.

In another method of treatment, autologous cytotoxic lymphocytes ortumor infiltrating lymphocytes may be obtained from a patient withcancer. The lymphocytes are grown in culture, and antigen-specificlymphocytes are expanded by culturing in the presence of the specificgene products alone or in combination with at least oneco-immunostimulatory molecule with cytokines. The antigen-specificlymphocytes are then infused back into the patient in an amounteffective to reduce or eliminate the tumors in the patient. Cancervaccines and their uses are further described in U.S. Pat. No.5,961,978; U.S. Pat. No. 5,993,829; U.S. Pat. No. 6,132,980; and WO00/38706.

Pharmaceutical Compositions and Uses

Pharmaceutical compositions can comprise polypeptides, receptors thatspecifically bind a polypeptide produced by a differentially expressedgene (e.g., antibodies, or polynucleotides (including antisensenucleotides and ribozymes) of the claimed invention in a therapeuticallyeffective amount. The compositions can be used to treat primary tumorsas well as metastases of primary tumors. In addition, the pharmaceuticalcompositions can be used in conjunction with conventional methods ofcancer treatment, e.g., to sensitize tumors to radiation or conventionalchemotherapy.

Where the pharmaceutical composition comprises a receptor (such as anantibody) that specifically binds to a gene product encoded by adifferentially expressed gene, the receptor can be coupled to a drug fordelivery to a treatment site or coupled to a detectable label tofacilitate imaging of a site comprising cancer cells. Methods forcoupling antibodies to drugs and detectable labels are well known in theart, as are methods for imaging using detectable labels.

The term “therapeutically effective amount” as used herein refers to anamount of a therapeutic agent to treat, ameliorate, or prevent a desireddisease or condition, or to exhibit a detectable therapeutic orpreventative effect. The effect can be detected by, for example,chemical markers or antigen levels. Therapeutic effects also includereduction in physical symptoms, such as decreased body temperature.

The precise effective amount for a subject will depend upon thesubject's size and health, the nature and extent of the condition, andthe therapeutics or combination of therapeutics selected foradministration. Thus, it is not useful to specify an exact effectiveamount in advance. However, the effective amount for a given situationis determined by routine experimentation and is within the judgment ofthe clinician. For purposes of the present invention, an effective dosewill generally be from about 0.01 mg/kg to 50 mg/kg or 0.05 mg/kg toabout 10 mg/kg of the DNA constructs in the individual to which it isadministered.

A pharmaceutical composition can also contain a pharmaceuticallyacceptable carrier. The term “pharmaceutically acceptable carrier”refers to a carrier for administration of a therapeutic agent, such asantibodies or a polypeptide, genes, and other therapeutic agents. Theterm refers to any pharmaceutical carrier that does not itself inducethe production of antibodies harmful to the individual receiving thecomposition, and which can be administered without undue toxicity.Suitable carriers can be large, slowly metabolized macromolecules suchas proteins, polysaccharides, polylactic acids, polyglycolic acids,polymeric amino acids, amino acid copolymers, lipid aggregates andinactive virus particles. Such carriers are well known to those ofordinary skill in the art. Pharmaceutically acceptable carriers intherapeutic compositions can include liquids such as water, saline,glycerol and ethanol. Auxiliary substances, such as wetting oremulsifying agents, pH buffering substances, and the like, can also bepresent in such vehicles.

Typically, the therapeutic compositions are prepared as injectables,either as liquid solutions or suspensions; solid forms suitable forsolution in, or suspension in, liquid vehicles prior to injection canalso be prepared. Liposomes are included within the definition of apharmaceutically acceptable carrier. Pharmaceutically acceptable saltscan also be present in the pharmaceutical composition, e.g., mineralacid salts such as hydrochlorides, hydrobromides, phosphates, sulfates,and the like; and the salts of organic acids such as acetates,propionates, malonates, benzoates, and the like. A thorough discussionof pharmaceutically acceptable excipients is available in Remington: TheScience and Practice of Pharmacy (1995) Alfonso Gennaro, Lippincott,Williams, & Wilkins.

Delivery Methods

Once formulated, the compositions contemplated by the invention can be(1) administered directly to the subject (e.g., as polynucleotide,polypeptides, small molecule agonists or antagonists, and the like); or(2) delivered ex vivo, to cells derived from the subject (e.g., as in exvivo gene therapy). Direct delivery of the compositions will generallybe accomplished by parenteral injection, e.g., subcutaneously,intraperitoneally, intravenously or intramuscularly, intratumoral or tothe interstitial space of a tissue. Other modes of administrationinclude oral and pulmonary administration, suppositories, andtransdermal applications, needles, and gene guns or hyposprays. Dosagetreatment can be a single dose schedule or a multiple dose schedule.

Methods for the ex vivo delivery and reimplantation of transformed cellsinto a subject are known in the art and described in e.g., InternationalPublication No. WO 93/14778. Examples of cells useful in ex vivoapplications include, for example, stem cells, particularlyhematopoetic, lymph cells, macrophages, dendritic cells, or tumor cells.Generally, delivery of nucleic acids for both ex vivo and in vitroapplications can be accomplished by, for example, dextran-mediatedtransfection, calcium phosphate precipitation, polybrene mediatedtransfection, protoplast fusion, electroporation, encapsulation of thepolynucleotide(s) in liposomes, and direct microinjection of the DNAinto nuclei, all well known in the art.

Once differential expression of a gene corresponding to a polynucleotidedescribed herein has been found to correlate with a proliferativedisorder, such as neoplasia, dysplasia, and hyperplasia, the disordercan be amenable to treatment by administration of a therapeutic agentbased on the provided polynucleotide, corresponding polypeptide or othercorresponding molecule (e.g., antisense, ribozyme, etc.). In otherembodiments, the disorder can be amenable to treatment by administrationof a small molecule drug that, for example, serves as an inhibitor(antagonist) of the function of the encoded gene product of a genehaving increased expression in cancerous cells relative to normal cellsor as an agonist for gene products that are decreased in expression incancerous cells (e.g., to promote the activity of gene products that actas tumor suppressors).

The dose and the means of administration of the inventive pharmaceuticalcompositions are determined based on the specific qualities of thetherapeutic composition, the condition, age, and weight of the patient,the progression of the disease, and other relevant factors. For example,administration of polynucleotide therapeutic composition agents includeslocal or systemic administration, including injection, oraladministration, particle gun or catheterized administration, and topicaladministration. In general, the therapeutic polynucleotide compositioncontains an expression construct comprising a promoter operably linkedto a polynucleotide of at least 12, 22, 25, 30, or 35 contiguous nt ofthe polynucleotide disclosed herein. Various methods can be used toadminister the therapeutic composition directly to a specific site inthe body. For example, a small metastatic lesion is located and thetherapeutic composition injected several times in several differentlocations within the body of the tumor. Alternatively, arteries whichserve a tumor are identified, and the therapeutic composition injectedinto such an artery, in order to deliver the composition directly intothe tumor. A tumor that has a necrotic center is aspirated and thecomposition injected directly into the now empty center of the tumor.The antisense composition is directly administered to the surface of thetumor, for example, by topical application of the composition. X-rayimaging is used to assist in certain of the above delivery methods.

Targeted delivery of therapeutic compositions containing an antisensepolynucleotide, subgenomic polynucleotides, or antibodies to specifictissues can also be used. Receptor-mediated DNA delivery techniques aredescribed in, for example, Findeis et al., Trends Biotechnol. (1993)11:202; Chiou et al., Gene Therapeutics: Methods And Applications OfDirect Gene Transfer (J. A. Wolff, ed.) (1994); Wu et al., J. Biol.Chem. (1988) 263:621; Wu et al., J. Biol. Chem. (1994) 269:542; Zenke etal., Proc. Natl. Acad. Sci. (USA) (1990) 87:3655; Wu et al., J. Biol.Chem. (1991) 266:338. Therapeutic compositions containing apolynucleotide are administered in a range of about 100 ng to about 200mg of DNA for local administration in a gene therapy protocol.Concentration ranges of about 500 ng to about 50 mg, about 1 μg to about2 mg, about 5 μg to about 500 μg, and about 20 μg to about 100 μg of DNAcan also be used during a gene therapy protocol. Factors such as methodof action (e.g., for enhancing or inhibiting levels of the encoded geneproduct) and efficacy of transformation and expression areconsiderations that will affect the dosage required for ultimateefficacy of the antisense subgenomic polynucleotides.

The therapeutic polynucleotides and polypeptides of the presentinvention can be delivered using gene delivery vehicles. The genedelivery vehicle can be of viral or non-viral origin (see generally,Jolly, Cancer Gene Therapy (1994) 1:51; Kimura, Human Gene Therapy(1994) 5:845; Connelly, Human Gene Therapy (1995) 1:185; and Kaplitt,Nature Genetics (1994) 6:148). Expression of such coding sequences canbe induced using endogenous mammalian or heterologous promoters.Expression of the coding sequence can be either constitutive orregulated.

Viral-based vectors for delivery of a desired polynucleotide andexpression in a desired cell are well known in the art. Exemplaryviral-based vehicles include, but are not limited to, recombinantretroviruses (see, e.g., WO 90/07936; WO 94/03622; WO 93/25698; WO93/25234; U.S. Pat. No. 5,219,740; WO 93/11230; WO 93/10218; U.S. Pat.No. 4,777,127; GB Patent No. 2,200,651; EP 0 345 242; and WO 91/02805),alphavirus-based vectors (e.g., Sindbis virus vectors, Semliki forestvirus (ATCC VR-67; ATCC VR-1247), Ross River virus (ATCC VR-373; ATCCVR-1246) and Venezuelan equine encephalitis virus (ATCC VR-923; ATCCVR-1250; ATCC VR 1249; ATCC VR-532), and adeno-associated virus (AAV)vectors (see, e.g., WO 94/12649, WO 93/03769; WO 93/19191; WO 94/28938;WO 95/11984 and WO 95/00655). Administration of DNA linked to killedadenovirus as described in Curiel, Hum. Gene Ther. (1992) 3:147 can alsobe employed.

Non-viral delivery vehicles and methods can also be employed, including,but not limited to, polycationic condensed DNA linked or unlinked tokilled adenovirus alone (see, e.g., Curiel, Hum. Gene Ther. (1992)3:147); ligand-linked DNA (see, e.g., Wu, J. Biol. Chem. (1989)264:16985); eukaryotic cell delivery vehicles cells (see, e.g., U.S.Pat. No. 5,814,482; WO 95/07994; WO 96/17072; WO 95/30763; and WO97/42338) and nucleic charge neutralization or fusion with cellmembranes. Naked DNA can also be employed. Exemplary naked DNAintroduction methods are described in WO 90/11092 and U.S. Pat. No.5,580,859. Liposomes that can act as gene delivery vehicles aredescribed in U.S. Pat. No. 5,422,120; WO 95/13796; WO 94/23697; WO91/14445; and EP 0524968. Additional approaches are described in Philip,Mol. Cell. Biol. (1994) 14:2411, and in Woffendin, Proc. Natl. Acad.Sci. (1994) 91:1581.

Tumor Classification and Patient Stratification

The invention further provides for methods of classifying tumors, andthus grouping or “stratifying” patients, according to the expressionprofile of selected differentially expressed genes in a tumor. Theexpression patterns of differentially expressed genes can be analyzedfor correlation with the expression patterns of other differentiallyexpressed genes in a single tumor type or across tumor types. Genes thatdemonstrate consistent correlation can be grouped together, e.g., genesare grouped together where if one gene is overexpressed in a tumor, asecond gene is also usually overexpressed. Tumors can then be classifiedaccording to the expression profile of one or more genes selected fromone or more groups.

For example, a colon tumor can be classified according to expressionlevel of a gene product of one or more genes selected from one or moreof the following groups: 1) Group I, which comprises the genes IGF2,TTK, MAPKAPK2, MARCKS, BBS2, CETN2 CGI-148 protein, FGFR4, FHL3,FLJ22066, KIP2, MGC:29604, NQO2, and OGG1; and 2) Group II, whichcomprises the genes IFITM (1-8U; 1-8D; 9-27), ITAK, and BIRC3/H-IAP1.

A Group I-type colon tumor has increased expression of at least one,usually at least two, more usually at least three, even more usually atleast four, preferably at least five, more preferably at least six ormore, but usually not more than 12, 10, or 8, Group I genes relative toa non-cancerous colon cell, where the expression is increased at leastabout 1.5-fold, at least about 2-fold, at least about 5-fold, or atleast about 10-fold, and can be as high 50-fold, but is usually not morethan 20-fold or 30-fold.

A Group II-type colon tumor is increased in expression of at least one,usually at least two, more usually at least three, Group II genesrelative to a non-cancerous colon cells, where the expression isincreased at least about 1.5-fold, at least about 2-fold, at least about5-fold, or at least about 10-fold, and can be as high 50-fold, but isusually not more than 20-fold or 30-fold.

A Group I+II-type colon tumor is increased in expression of at leastone, usually at least two, more usually at least three, even moreusually at least four, preferably at least five, more preferably atleast six or more, but usually not more than 12, 10, or 8, Group I genesrelative to a non-cancerous colon cell, and has increased expression ofat least one, usually at least two, more usually at least three, GroupII genes relative to a non-cancerous colon cells, where expression ofboth the Group I and Group II genes is increased at least about1.5-fold, at least about 2-fold, at least about 5-fold, or at leastabout 10-fold, and can be as high 50-fold, but is usually not more than20-fold or 30-fold.

The tumor of each patient in a pool of potential patients for a clinicaltrial can be classified as described above. Patients having similarlyclassified tumors can then be selected for participation in aninvestigative or clinical trial of a cancer therapeutic where ahomogeneous population is desired. The tumor classification of a patientcan also be used in assessing the efficacy of a cancer therapeutic in aheterogeneous patient population. Thus, comparison of an individual'sexpression profile to the population profile for a type of cancer,permits the selection or design of drugs or other therapeutic regimensthat are expected to be safe and efficacious for a particular patient orpatient population (i.e., a group of patients having the same type ofcancer).

In addition, the ability to target populations expected to show the mostclinical benefit, based on expression profile can enable: 1) therepositioning of already marketed drugs; 2) the rescue of drugcandidates whose clinical development has been discontinued as a resultof safety or efficacy limitations, which are patient subgroup-specific;and 3) an accelerated and less costly development for candidatetherapeutics and more optimal drug labeling (e.g. since measuring theeffect of various doses of an agent on patients with a particularexpression profile is useful for optimizing effective dose).

A certain embodiment of the invention is based on the discovery of genesdifferentially expressed in cancerous colon cells relative to normalcells, particularly metastatic or pre-metastatic cancerous colon cellsrelative to normal cells of the same tissue type. The genes ofparticular interest are those described in the Examples below. Theinvention is further based on the discovery that colon tumors can beclassified according to the expression pattern of one or more of genes,and that patients can thus be classified and diagnosed, and therapyselected accordingly, according to these expression patterns. Thegene(s) for analysis of expression of a gene product encoded by at leastone gene selected from at least one of the following groups: 1) Group I,which comprises the genes IGF2, TTK, MAPKAPK2, MARCKS, BBS2, CETN2CGI-148 protein, FGFR4, FHL3, FLJ22066, KIP2, MGC:29604, NQO2, and OGG1;and 2) Group II, which comprises the genes IFITM (1-8U; 1-8D; 9-27),ITAK, and BIRC3/H-IAP1. A tumor can then be classified as a GroupI-type, Group II-type, or Group I+II-type tumor based on the expressionprofile of the tumor. The expression patterns associated with coloncancer, and which provide the basis for tumor classification and patientstratification, are described in the Examples below.

The methods of the invention can be carried out using any suitable probefor detection of a gene product that is differentially expressed incolon cancer cells. For example, mRNA (or cDNA generated from mRNA)expressed from a differentially expressed gene can be detected usingpolynucleotide probes. In another example, the differentially expressedgene product is a polypeptide, which polypeptides can be detected using,for example, antibodies that specifically bind such polypeptides or anantigenic portion thereof.

The present invention relates to methods and compositions useful indiagnosis of colon cancer, design of rational therapy, and the selectionof patient populations for the purposes of clinical trials. Theinvention is based on the discovery that colon tumors of a patient canbe classified according to an expression profile of one or more selectedgenes, which genes are differentially expressed in tumor cells relativeto normal cells of the same tissue. Polynucleotides that correspond tothe selected differentially expressed genes can be used in diagnosticassays to provide for diagnosis of cancer at the molecular level, and toprovide for the basis for rational therapy (e.g., therapy is selectedaccording to the expression pattern of a selected set of genes in thetumor). The gene products encoded by differentially expressed genes canalso serve as therapeutic targets, and candidate agents effectiveagainst such targets screened by, for example, analyzing the ability ofcandidate agents to modulate activity of differentially expressed geneproducts.

In one aspect, the selected gene(s) for tumor cell (and thus patient)analysis of expression of a gene product encoded by at least one geneselected from at least one of the following groups: 1) Group I, whichcomprises the genes IGF2, TTK, MAPKAPK2, MARCKS, BBS2, CETN2 CGI-148protein, FGFR4, FHL3, FLJ22066, KIP2, MGC:29604, NQO2, and OGG1; and 2)Group II, which comprises the genes IFITM (1-8U; 1-8D; 9-27), ITAK, andBIRC3/H-IAP1.

In another aspect, the invention provides a method for classifying atumor that shares selected characteristics with respect to a tumorexpression profile. In one embodiment, the invention provides a methodfor classifying a tumor according to an expression profile of one ormore genes comprising detecting expression of at least a first Group Igene in a test colon cell sample. Detection of increased expression ofthe first gene in the test colon cell sample relative to expression ofthe gene in a control non-cancer cell sample indicates that the tumor isa Group I-type tumor.

In one embodiment, the first Group I gene is an IGF2 gene. In otherspecific embodiments, the method further comprises detecting expressionof a second Group I gene in the test colon cell sample. Detection ofincreased expression of the first and second genes in the test coloncell sample relative to expression of the first and second genes,respectively, in a control non-cancer cell sample indicates that thetumor is a Group I-type tumor.

In another embodiment, the method further comprises detecting expressionof a second and third Group I gene in the test colon cell sample.Detection of increased expression of the first, second, and third genesin the test colon cell sample relative to expression of the first,second, and third genes, respectively, in a control non-cancer cellsample indicates that the tumor is a Group I-type tumor. In otherembodiments, the expression of the gene(s) is increased about 1.5-fold,about 2-fold, about 5-fold, or about 10-fold in the test sample relativeto the control sample.

In another embodiment, the invention provides a method for classifying atumor according to an expression profile of one or more genes comprisingdetecting expression of at least a first Group II gene in a test coloncell sample. Detection of increased expression of the first gene in thetest colon cell sample relative to expression of the gene in a controlnon-cancer cell sample indicates that the tumor is a Group II-typetumor.

In another embodiment, the first Group II gene is a member of the IFITMfamily of genes. In other specific embodiments, the method furthercomprises detecting expression of a second Group II gene in the testcolon cell sample. Detection of increased expression of the first andsecond genes in the test colon cell sample relative to expression of thefirst and second genes, respectively, in a control non-cancer cellsample indicates that the tumor is a Group II-type tumor. In otherembodiments, the expression of the gene(s) is increased about 1.5-fold,about 2-fold, about 5-fold, or about 10-fold in the test sample relativeto the control sample. In yet other specific embodiments, the firstGroup II gene is 1-8U, 1-8D, or 9-27.

In another embodiment, the invention provides a method for classifying atumor according to an expression profile of two or more genes, themethod comprising analyzing a test colon cell sample for expression ofat least one Group I gene and at least one Group II gene. Detection ofincreased expression of the at least one Group I gene and the at leastone Group II gene in the test cell sample relative to expression of theat least one Group I gene and the at least one Group II gene,respectively, in a control non-cancer cell sample indicates the tumor isa Group I+II-type tumor. In other embodiments, the Group I gene is anIGF2 gene and the Group II gene is a member of the IFITM family ofgenes. In yet other embodiments, the expression of the genes isincreased about 1.5-fold, about 2-fold, about 5-fold, or about 10-foldin the test sample relative to the control sample.

In another aspect, the invention provides methods for selection of apatient population having a tumor that shares selected characteristicswith respect to a tumor expression profile. This method, referred toherein as “patient stratification,” can be used to improve the design ofa clinical trial by providing a patient population that is morehomogenous with respect to the tumor type that is to be tested forresponsiveness to a new therapy; and in selecting the best therapeuticregiment for a patient in view of an expression profile of the subject'stumor (e.g., rational therapy).

In another aspect, the invention provides a method for selecting anindividual for inclusion in a clinical trial, the method comprising thesteps of: detecting a level of expression of a gene product in a testcolon cell sample or serum obtained from a subject, the gene productbeing encoded by at least one gene selected from the group consisting ofIGF2, TTK, MAPKAPK2, MARCKS, BBS2, CETN2 CGI-148 protein, FGFR4, FHL3,FLJ22066, KIP2, MGC:29604, NQO2, and OGG1; and comparing the level ofexpression of the gene product in the test sample to a level ofexpression in a normal colon cell; wherein detection of a level ofexpression of the gene product that is significantly higher in the testsample than in a normal cell is a positive indicator for inclusion ofthe subject in the test population for the clinical trial.

In another aspect the invention provides a method for selecting anindividual for inclusion in a clinical trial, the method comprising thesteps of: detecting a level of expression of a gene product in a testcolon cell sample obtained from a subject, the gene product beingencoded by at least one gene selected from the group consisting of:IFITM (1-8U; 1-8D; 9-27), ITAK, and BIRC3/H-IAP1; and comparing thelevel of expression of the gene product in the test sample to a level ofexpression in a normal colon cell; wherein detection of a level ofexpression of the gene product that is significantly higher in the testsample than in a normal cell is a positive indicator for inclusion ofthe subject in the test population for the clinical trial.

In related aspects the invention provides methods of reducing growth ofcancerous colon cells by modulation of expression of one or more geneproducts corresponding to a gene selected from: 1) Group I, whichcomprises the genes IGF2, TTK, MAPKAPK2, MARCKS, BBS2, CETN2 CGI-148protein, FGFR4, FHL3, FLJ22066, KIP2, MGC:29604, NQO2, and OGG1; and 2)Group II, which comprises the genes IFITM (1-8U; 1-8D; 9-27), ITAK, andBIRC3/H-IAP1. These methods are useful for treating colon cancer.

In another aspect, the present invention provides methods for diseasedetection by analysis of gene expression. In general, diagnostic andprognostic methods of the invention can involve obtaining a test cellfrom a subject, e.g., colon cells; detecting the level of expression ofany one gene or a selected set of genes in the test cell, where thegene(s) are differentially expressed in a colon tumor cell relative to anormal colon cell; and comparing the expression levels of the gene(s) inthe test cell to a control level (e.g., a level of expression in anormal (non-cancerous) colon cell). Detection of a level of expressionin the test cell that differs from that found in a normal cell indicatesthat the test cell is a cancerous cell. The method of the inventionpermits, for example, detection of a small increase or decrease in geneproduct production from a gene whose overexpression or underexpression(compared to a reference gene) is associated with cancer or thepredisposition for a cancer.

In another aspect the invention provides a method for detecting acancerous colon cell comprising contacting a sample obtained from a testcolon cell with a probe for detection of a gene product of a genedifferentially expressed in colon cancer, wherein the gene correspondsto a polynucleotide having a sequence selected from the group consistingof SEQ ID NOS: 1-20, and where contacting is for a time sufficient forbinding of the probe to the gene product; and comparing a level ofbinding of the probe to the sample with a level of probe binding to acontrol sample obtained from a control colon cell, wherein the controlcolon cell is of known cancerous state. An increased level of binding ofthe probe in the test colon cell sample relative to the level of bindingin a control sample is indicative of the cancerous state of the testcolon cell. In specific embodiments, the probe is a polynucleotide probeand the gene product is nucleic acid. In other specific embodiments, thegene product is a polypeptide. In further embodiments, the gene productor the probe is immobilized on an array.

In another aspect, the invention provides a method for assessing thecancerous phenotype (e.g., metastasis, aberrant cellular proliferation,and the like) of a colon cell comprising detecting expression of a geneproduct in a test colon cell sample, wherein the gene comprises asequence selected from the group consisting of SEQ ID NOS: 1-20; andcomparing a level of expression of the gene product in the test coloncell sample with a level of expression of the gene in a control cellsample. Comparison of the level of expression of the gene in the testcell sample relative to the level of expression in the control cellsample is indicative of the cancerous phenotype of the test cell sample.In specific embodiments, detection of expression of the gene is bydetecting a level of an RNA transcript in the test cell sample. In otherspecific embodiments detection of expression of the gene is by detectinga level of a polypeptide in a test sample.

In another aspect, the invention provides a method for suppressing orinhibiting a cancerous phenotype of a cancerous cell, the methodcomprising introducing into a mammalian cell an antisense polynucleotidefor inhibition of expression of a gene comprising a sequence selectedfrom the group consisting of SEQ ID NOS: 1-20. Inhibition of expressionof the gene inhibits development of a cancerous phenotype in the cell.In specific embodiments, the cancerous phenotype is metastasis, aberrantcellular proliferation relative to a normal cell, or loss of contactinhibition of cell growth.

In another aspect, the invention provides a method for assessing thetumor burden of a subject, the method comprising detecting a level of adifferentially expressed gene product in a test sample from a subjectsuspected of or having a tumor, the differentially expressed geneproduct comprising a sequence selected from the group consisting of SEQID NOS: 1-20. Detection of the level of the gene product in the testsample is indicative of the tumor burden in the subject.

In another aspect, the invention provides a method for identifying agene product as a target for a cancer therapeutic, the method comprisingcontacting a cancerous cell expressing a candidate gene product with ananti-cancer agent, wherein the candidate gene product corresponds to asequence selected from the group consisting of SEQ ID NOS: 1-20; andanalyzing the effect of the anti-cancer agent upon a biological activityof the candidate gene product and upon a cancerous phenotype of thecancerous cell. Modulation of the biological activity of the candidategene product and modulation of the cancerous phenotype of the cancerouscell indicates the candidate gene product is a target for a cancertherapeutic. In specific embodiments, the cancerous cell is a cancerouscolon cell. In other specific embodiments, the inhibitor is an antisenseoligonucleotide. In further embodiments, the cancerous phenotype isaberrant cellular proliferation relative to a normal cell, or colonyformation due to loss of contact inhibition of cell growth.

In another aspect, the invention provides a method for identifyingagents that decrease biological activity of a gene productdifferentially expressed in a cancerous cell, the method comprisingcontacting a candidate agent with a differentially expressed geneproduct, the differentially expressed gene product corresponding to asequence selected from the group consisting of SEQ ID NOS: 1-20; anddetecting a decrease in a biological activity of the gene productrelative to a level of biological activity of the gene product in theabsence of the candidate agent. In specific embodiments, the detectingis by detection of a decrease in expression of the differentiallyexpressed gene product. In other specific embodiments, the gene productis mRNA or cDNA prepared from the mRNA gene product. In furtherembodiments, the gene product is a polypeptide.

In all embodiments of the invention, analysis of expression of a geneproduct of a selected gene can be accomplished by analysis of genetranscription (e.g., by generating cDNA clones from mRNAs isolated froma cell suspected of being cancerous and comparing the number of cDNAclones corresponding to the gene in the sample relative to a number ofclones present in a non-cancer cell of the same tissue type), detectionof an encoded gene product (e.g., assessing a level of polypeptideencoded by a selected gene present in the test cell suspected of beingcancerous relative to a level of the polypeptide in a non-cancer cell ofthe same tissue type), detection of a biological activity of a geneproduct encoded by a selected gene, and the like.

In all embodiments of the invention, comparison of gene productexpression of a selected gene in a tumor cell can involve, for example,comparison to an “internal” control cell (e.g., a non-cancer cell of thesame tissue type obtained from the same patient from whom the samplesuspected of having a tumor cell was obtained), comparison to a controlcell analyzed in parallel in the assay (e.g., a non-cancer cell,normally of the same tissue type as the test cell or a cancerous cell,normally of the same tissue type as the test cell), or comparison to alevel of gene product expression known to be associated with a normalcell or a cancerous cell, normally of the same tissue type (e.g., alevel of gene product expression is compared to a known level or rangeof levels of gene product expression for a normal cell or a cancerouscell, which can be provided in the form of, for example, a standard).

The sequences disclosed in this patent application were disclosed inseveral earlier patent applications. The relationship between the SEQ IDNOS in those earlier applications and the SEQ ID NOS disclosed herein isas follows. SEQ ID NOS: 1-321 of parent case 15805CON (Ser. No.10/616,900, filed Jul. 9, 2003) correspond to SEQ ID NOS: 1-321 of thepresent application. SEQ ID NOS: 1-20 of parent case 16335 (Ser. No.10/081,519, filed Feb. 21, 2002) correspond to SEQ ID NOS: 322-341 ofthe present application. SEQ ID NOS: 1-2164 of parent case 18095 (Ser.No. 10/310,673, filed Dec. 4, 2002) correspond to SEQ ID NOS: 342-2505of the present application. SEQ ID NOS: 1-516 of parent case 17767 (Ser.No. 10/501,187, filed Jul. 8, 2004) correspond to SEQ ID NOS: 2506-3021of the present application. SEQ ID NOS: 1-1303 of parent case 16336(Ser. No. 10/081,124, filed Feb. 21, 2002) correspond to SEQ ID NOS:3022-4324 of the present application. SEQ ID NOS: 1-9672 of parent case18376 (U.S. Pat. No. 0,415,421, filed May 13, 2004) correspond to SEQ IDNOS: 4325-13996 of the present application.

The disclosures of all prior U.S. applications to which the presentapplication claims priority, which includes those U.S. applicationsreferenced in the table above as well as their respective priorityapplications, are each incorporated herein by referenced in theirentireties for all purposes, including the disclosures found in theSequence Listings, tables, figures and Examples.

EXAMPLES

The following examples are put forth so as to provide those of ordinaryskill in the art with a complete disclosure and description of how tomake and use the present invention, and are not intended to limit thescope of what the inventors regard as their invention nor are theyintended to represent that the experiments below are all or the onlyexperiments performed. Efforts have been made to ensure accuracy withrespect to numbers used (e.g. amounts, temperature, etc.) but someexperimental errors and deviations should be accounted for. Unlessindicated otherwise, parts are parts by weight, molecular weight isweight average molecular weight, temperature is in degrees Centigrade,and pressure is at or near atmospheric.

Example 1 Source of Biological Materials and Isolation ofPolynucleotides Expressed by the Biological Materials

Candidate polynucleotides that may represent genes differentiallyexpressed in cancer were obtained from both publicly available sourcesand from cDNA libraries generated from selected cell lines and patienttissues. In order to obtain the latter polynucleotides, mRNA wasisolated from several selected cell lines and patient tissues, and usedto construct cDNA libraries. The cells and tissues that served assources for these cDNA libraries are summarized in Table 1 below.

TABLE 1 Description of cDNA Libraries Number of Clones Library in (lib#) Description Library 1 Human Colon Cell Line Km12 L4: High Metastatic308731 Potential (derived from Km12C) 2 Human Colon Cell Line Km12C: LowMetastatic 284771 Potential 3 Human Breast Cancer Cell Line MDA-MB-231:High 326937 Metastatic Potential; micro-mets in lung 4 Human BreastCancer Cell Line MCF7: Non 318979 Metastatic 8 Human Lung Cancer CellLine MV-522: High 223620 Metastatic Potential 9 Human Lung Cancer CellLine UCP-3: Low 312503 Metastatic Potential 12 Human microvascularendothelial cells (HMVEC) - 41938 UNTREATED (PCR (OligodT) cDNA library)13 Human microvascular endothelial cells (HMVEC) - 42100 bFGF TREATED(PCR (OligodT) cDNA library) 14 Human microvascular endothelial cells(HMVEC) - 42825 VEGF TREATED (PCR (OligodT) cDNA library) 15 NormalColon - UC#2 Patient (MICRODISSECTED 248436 PCR (OligodT) cDNA library)16 Colon Tumor - UC#2 Patient (MICRODISSECTED 263206 PCR (OligodT) cDNAlibrary) 17 Liver Metastasis from Colon Tumor of UC#2 Patient 266482(MICRODISSECTED PCR (OligodT) cDNA library) 18 Normal Colon - UC#3Patient (MICRODISSECTED 36216 PCR (OligodT) cDNA library) 19 ColonTumor - UC#3 Patient (MICRODISSECTED 41388 PCR (OligodT) cDNA library)20 Liver Metastasis from Colon Tumor of UC#3 Patient 30956(MICRODISSECTED PCR (OligodT) cDNA library) 21 GRRpz Cells derived fromnormal prostate epithelium 164801 22 WOca Cells derived from GleasonGrade 4 prostate 162088 cancer epithelium 23 Normal Lung Epithelium ofPatient #1006 306197 (MICRODISSECTED PCR (OligodT) cDNA library) 24Primary tumor, Large Cell Carcinoma of Patient 309349 #1006(MICRODISSECTED PCR (OligodT) cDNA library)

The human colon cancer cell line Km12L4-A (Morikawa, et al., CancerResearch (1988) 48:6863) is derived from the KM12C cell line. The KM12Ccell line (Morikawa et al. Cancer Res. (1988) 48:1943-1948), which ispoorly metastatic (low metastatic) was established in culture from aDukes' stage B₂ surgical specimen (Morikawa et al. Cancer Res. (1988)48:6863). The KML4-A is a highly metastatic subline derived from KM12C(Yeatman et al. Nucl. Acids. Res. (1995) 23:4007; Bao-Ling et al. Proc.Annu. Meet. Am. Assoc. Cancer. Res. (1995) 21:3269). The KM12C andKM12C-derived cell lines (e.g., KM12L4, KM12L4-A, etc.) arewell-recognized in the art as a model cell line for the study of coloncancer (see, e.g., Moriakawa et al., supra; Radinsky et al. Clin. CancerRes. (1995) 1:19; Yeatman et al., (1995) supra; Yeatman et al. Clin.Exp. Metastasis (1996)14:246).

The MDA-MB-231 cell line (Brinkley et al. Cancer Res. (1980)40:3118-3129) was originally isolated from pleural effusions (Cailleau,J. Natl. Cancer. Inst. (1974) 53:661), is of high metastatic potential,and forms poorly differentiated adenocarcinoma grade II in nude miceconsistent with breast carcinoma. The MCF7 cell line was derived from apleural effusion of a breast adenocarcinoma and is non-metastatic. TheMV-522 cell line is derived from a human lung carcinoma and is of highmetastatic potential. The UCP-3 cell line is a low metastatic human lungcarcinoma cell line; the MV-522 is a high metastatic variant of UCP-3.These cell lines are well-recognized in the art as models for the studyof human breast and lung cancer (see, e.g., Chandrasekaran et al.,Cancer Res. (1979) 39:870 (MDA-MB-231 and MCF-7); Gastpar et al., J MedChem (1998) 41:4965 (MDA-MB-231 and MCF-7); Ranson et al., Br J Cancer(1998) 77:1586 (MDA-MB-231 and MCF-7); Kuang et al., Nucleic Acids Res(1998) 26:1116 (MDA-MB-231 and MCF-7); Varki et al., Int J Cancer (1987)40:46 (UCP-3); Varki et al., Tumour Biol. (1990)11:327; (MV-522 andUCP-3); Varki et al., Anticancer Res. (1990) 10:637; (MV-522); Kelner etal., Anticancer Res (1995)15:867 (MV-522); and Zhang et al., AnticancerDrugs (1997) 8:696 (MV522)).

The samples of libraries 15-20 are derived from two different patients(UC#2, and UC#3). The bFGF-treated HMVEC were prepared by incubationwith bFGF at 10 ng/ml for 2 hrs; the VEGF-treated HMVEC were prepared byincubation with 20 ng/ml VEGF for 2 hrs. Following incubation with therespective growth factor, the cells were washed and lysis buffer addedfor RNA preparation. The GRRpz and WOca cell lines were provided by Dr.Donna M. Peehl, Department of Medicine, Stanford University School ofMedicine. GRRpz was derived from normal prostate epithelium. The WOcacell line is a Gleason Grade 4 cell line.

Characterization of Sequences in the Libraries

The sequences of the isolated polynucleotides were first masked toeliminate low complexity sequences using the XBLAST masking program(Clayerie “Effective Large-Scale Sequence Similarity Searches,” In:Computer Methods for Macromolecular Sequence Analysis, Doolittle, ed.,Meth. Enzymol. 266:212-227 Academic Press, NY, N.Y. (1996); seeparticularly Clayerie, in “Automated DNA Sequencing and AnalysisTechniques” Adams et al., eds., Chap. 36, p. 267 Academic Press, SanDiego, 1994 and Clayerie et al. Comput. Chem. (1993) 17:191). Generally,masking does not influence the final search results, except to eliminatesequences of relative little interest due to their low complexity, andto eliminate multiple “hits” based on similarity to repetitive regionscommon to multiple sequences, e.g., Alu repeats. Masking resulted in theelimination of several sequences. The remaining sequences were then usedin a BLASTN vs. GenBank search. Gene assignment for the query sequenceswas determined based on best hit from the GenBank database; expectancyvalues are provided with the hit.

Summary of Polynucleotides Described Herein

Table 2 provides a summary of polynucleotides isolated as describedabove and identified as corresponding to a differentially expressed gene(see Example 2 below), as well as those polynucleotides obtained frompublicly available sources. Specifically, Table 2 provides: 1) the SEQID NO assigned to each sequence for use in the present specification; 2)the Candidate Identification Number (“CID”) to which the sequence isassigned and which number is based on the selection of the candidate forfurther evaluation in the differential expression in cancerous cellsrelative to normal cells; 3) the Sequence Name assigned to eachsequence; and 4) the name assigned to the sample or clone from which thesequence was isolated. The sequences corresponding to SEQ ID NOS areprovided in the Sequence Listing. Because at least some of the providedpolynucleotides represent partial mRNA transcripts, two or morepolynucleotides may represent different regions of the same mRNAtranscript and the same gene and/or may be contained within the sameclone. Thus, if two or more SEQ ID NOS are identified as belonging tothe same clone, then either sequence can be used to obtain thefull-length mRNA or gene. It should be noted that not all cDNA librariesdescribed above are represented on an array in the examples describedbelow.

TABLE 2 SEQ ID NO CID Sequence Name Sample Name or Clone Name 1 114016824.Seq M00003814C:C11 2 123 019.G3.sp6_128473 M00006883D:H12 3 114020.B11.sp6_128613 M00003814C:C11 4 1 1222317 I:1222317:15A02:C02 5 21227385 I:1227385:14B01:G05 6 3 1297179 I:1297179:05A02:F02 7 4 1298021I:1298021:05A01:G10 8 5 1358285 I:1358285:04A02:F11 9 6 1384823I:1384823:01B02:F08 10 7 1395918 I:1395918:04A01:G10 11 8 1402615I:1402615:09A02:E03 12 9 1421929 I:1421929:05A01:D02 13 10 1431819I:1431819:14B01:D05 14 11 1443877 I:1443877:03B02:B08 15 12 1450639I:1450639:03B02:E09 16 13 1480159 I:1480159:06B02:E03 17 14 1509602I:1509602:04A01:A11 18 15 1516301 I:1516301:05B01:C10 19 1671598.C19.gz43_212821 M00055583C:B07 20 16 1600586 I:1600586:05B02:F04 2117 1609538 I:1609538:06A02:F04 22 18 1613615 I:1613615:03B01:D10 23 191630804 I:1630804:06A02:F10 24 20 1633286 I:1633286:06A02:E04 25 211666080 I:1666080:07B02:D04 26 22 1699587 I:1699587:06A02:F11 27 231702266 I:1702266:02B01:D09 28 24 1712592 I:1712592:04A01:E03 29 251723834 I:1723834:01A01:C02 30 26 1743234 I:1743234:16B01:D09 31 1701744.K05.gz43_221934 M00056250C:B02 32 27 1749417 I:1749417:04A02:D10 3328 1749883 I:1749883:05B01:D04 34 29 1750782 I:1750782:02A01:A08 35 301758241 I:1758241:15B02:G04 36 31 1809385 I:1809385:02A02:G04 37 321810640 I:1810640:01A02:D06 38 33 1817434 I:1817434:02B01:C02 39 341833191 I:1833191:14A01:G05 40 35 1854245 I:1854245:02B02:E10 41 361854558 I:1854558:03A01:C11 42 37 1857563 I:1857563:05B02:D01 43 381920522 I:1920522:15B02:F02 44 39 1920650 I:1920650:16A01:B01 45 411923490 I:1923490:18B01:H08 46 42 1923769 I:1923769:16B01:F01 47 431926006 I:1926006:15A01:F09 48 44 1931371 I:1931371:02B02:D12 49 451960722 I:1960722:13B02:D11 50 46 1963753 I:1963753:18B01:E07 51 471965257 I:1965257:18B02:B04 52 48 1967543 I:1967543:16B02:F06 53 491968921 I:1968921:15A02:D06 54 50 1969044 I:1969044:18B01:E12 56 531996180 I:1996180:19B01:C11 57 54 2054678 I:2054678:19A01:F10 58 552055926 I:2055926:14A01:F11 59 56 2056395 I:2056395:13A02:B07 60 582060725 I:2060725:13A01:G10 61 59 2079906 I:2079906:01A02:A06 62 602152363 I:2152363:04A02:A08 63 63 2239819 I:2239819:04A02:B11 64 642359588 I:2359588:18A01:F03 65 65 2458926 I:2458926:03B01:C07 66 662483109 I:2483109:05A01:A06 67 67 2499479 I:2499479:05A01:D06 68 682499976 I:2499976:01B02:E09 70 71 2615513 I:2615513:04B01:D09 71 742675481 I:2675481:05A01:G06 73 100 268.H2.sp6_144757 M00001341B:A11 74105 270.B6.sp6_145073 M00001402B:C12 75 106 270.C6.sp6_145085M00001402C:B01 76 104 270.H3.sp6_145142 M00001393D:F01 77 75 2759046I:2759046:19B02:C05 78 76 2825369 I:2825369:07A02:F09 79 77 2840195I:2840195:01B02:G11 80 78 2902903 I:2902903:12A02:F02 81 79 2914605I:2914605:04B01:G06 82 80 2914719 I:2914719:04B02:B05 83 81 3229778I:3229778:02B01:B07 84 109 323.B1.sp6_145452 M00001489B:G04 85 110323.C3.sp6_145466 M00001496A:G03 86 111 324.H1.sp6_145716 M00001558C:B0687 121 325.H11.sp6_145918 M00005360A:A07 88 118 325.H4.sp6_145911M00004031B:D12 89 41 344.B2.sp6_146237 M00022742A:F08 90 139344.C4.sp6_146251 M00023363C:A04 91 83 3518380 I:3518380:16A01:B07 92 854072558 I:4072558:12B01:A07 93 117 414.A11.sp6_149879 M00003961B:H05 94113 414.F2.sp6_149930 M00001675B:G05 95 87 549299 I:549299:17B02:F06 9688 605019 I:605019:13B02:D03 97 89 620494 I:620494:16A01:C10 98 125626.D8.sp6_157447 M00007965C:G08 99 128 627.E8.sp6_157651 M00007987D:D04100 127 627.G6.sp6_157673 M00007985B:A03 101 129 628.D12.sp6_157835M00008049B:A12 102 130 634.H4.sp6_155966 M00008099D:A05 104 136642.C6.sp6_156292 M00022168B:F02 106 5 642.D8.sp6_156306 M00022180D:E11107 137 642.H11.sp6_156357 M00022215C:A10 108 138 653.A3.sp6_158944M00023283C:C06 109 141 655.B4.sp6_156470 M00023431B:A01 110 90 659143I:659143:16B01:E06 111 145 661.B5.sp6_159726 M00027066B:E09 112 91750899 I:750899:16A01:D04 113 92 763607 I:763607:16A01:E09 114 93 901317I:901317:16A01:G01 116 100 919.H2.SP6_168750 M00001341B:A11 118 123956.B04.sp6_177996 M00006883D:H12 119 94 956077 I:956077:14B01:H04 12095 970933 I:970933:14B01:D03 121 96 986558 I:986558:18A01:C09 122 98998612 I:998612:14B02:G06 123 103 A061.ga43_378496 M00001374A:A06 124103 A062.ga43_378497 M00001374A:A06 125 133 A121.ga43_378498M00022009A:A12 126 133 A122.ga43_378499 M00022009A:A12 130 115G022a.ga43_378503 M00003852B:C01 131 106 RTA00000179AF.k.22.1.SeqM00001402C:B01 132 113 RTA00000187AF.g.2.1.Seq M00001675B:G05 133 113RTA00000187AR.g.2.2.Seq M00001675B:G05 134 106 RTA00000348R.j.10.1.SeqM00001402C:B01 135 116 RTA00000588F.l.02.2.Seq M00003853B:G11 136 117RTA00000588F.o.23.1.Seq M00003961B:H05 138 123 RTA00000603F.d.06.1.SeqM00006883D:H12 140 140 RTA00000847F.n.19.3.Seq M00023371A:G03 141 143RTA00000922F.g.12.1.Seq M00026900D:F02 142 121 RTA00001042F.o.18.1.SeqM00005360A:A07 143 121 RTA00001064F.c.16.1.Seq M00005360A:A07 144 139RTA00001069F.c.03.1.Seq M00023363C:A04 145 112 RTA00002890F.d.16.1.P.SeqM00001600C:B11 147 166 RTA22200002F.b.15.1.P.Seq M00055435B:A12 148 167RTA22200003F.b.13.1.P.Seq M00055583C:B07 149 169RTA22200005F.d.14.1.P.Seq M00055873C:B06 150 30RTA22200007F.j.17.2.P.Seq M00056227B:G06 151 170RTA22200007F.m.02.1.P.Sequence M00056250C:B02 152 171RTA22200008F.a.24.1.P.Seq M00056301D:A04 153 171RTA22200008F.b.01.1.P.Seq M00056301D:A04 154 172RTA22200008F.b.22.1.P.Sequence M00056308A:F02 155 147RTA22200009F.b.03.2.P.Sequence M00042439D:C11 156 149RTA22200009F.c.22.2.P.Seq M00042756A:H02 157 150RTA22200009F.e.10.1.P.Seq M00042770D:G04 158 151RTA22200009F.i.17.2.P.Seq M00042818A:D05 159 173RTA22200009F.p.21.1.P.Seq M00056350B:B03 161 175RTA22200010F.k.02.1.P.Seq M00056478D:B07 162 176RTA22200010F.k.19.1.P.Seq M00056483D:G07 163 177RTA22200010F.m.13.1.P.Seq M00056500C:A07 164 178RTA22200011F.b.05.1.P.Seq M00056533D:G07 165 179RTA22200011F.b.09.1.P.Seq M00056534C:E08 166 180RTA22200011F.g.21.1.P.Seq M00056585B:F04 168 182RTA22200011F.l.06.1.P.Seq M00056619A:H02 169 183RTA22200011F.l.15.1.P.Seq M00056622B:F12 170 184RTA22200011F.m.13.1.P.Seq M00056632B:H10 171 185RTA22200011F.n.24.1.P.Seq M00056645C:D11 172 185RTA22200011F.o.01.1.P.Seq M00056645C:D11 173 186RTA22200011F.o.03.1.P.Seq M00056646B:F07 174 187RTA22200012F.c.01.1.P.Seq M00056679B:H03 176 189RTA22200012F.f.15.1.P.Seq M00056709B:D03 177 190RTA22200012F.i.14.1.P.Seq M00056728C:G02 179 192RTA22200013F.b.20.1.P.Seq M00056810A:A02 180 193RTA22200013F.c.06.1.P.Seq M00056812D:A08 181 194RTA22200013F.d.15.1.P.Seq M00056822A:E08 182 195RTA22200013F.o.17.1.P.Seq M00056908A:H05 183 196RTA22200013F.p.24.1.P.Seq M00056918C:F09 184 197RTA22200014F.b.18.1.P.Seq M00056937C:C10 185 197RTA22200014F.b.18.2.P.Seq M00056937C:C10 190 199RTA22200014F.j.08.1.P.Seq M00056992C:F12 191 199RTA22200014F.j.08.2.P.Seq M00056992C:F12 192 200RTA22200015F.a.18.1.P.Seq M00057044D:G03 193 176RTA22200015F.a.23.1.P.Seq M00057046A:G09 194 201RTA22200015F.f.17.1.P.Seq M00057081B:H03 196 118RTA22200015F.k.10.1.P.Seq M00057112B:E11 198 204RTA22200015F.m.15.1.P.Seq M00057127B:B09 200 206RTA22200016F.i.21.1.P.Seq M00057231A:G04 201 207RTA22200016F.k.08.1.P.Seq M00057241C:F03 202 152RTA22200019F.h.04.1.P.Seq M00054500D:C08 204 151RTA22200019F.j.24.1.P.Seq M00054520A:D04 205 151RTA22200019F.k.01.1.P.Seq M00054520A:D04 206 153RTA22200019F.m.05.1.P.Seq M00054538C:C01 207 154RTA22200020F.i.12.1.P.Seq M00054639D:F05 208 155RTA22200020F.j.09.1.P.Seq M00054647A:A09 209 156RTA22200020F.j.24.1.P.Seq M00054650D:E04 210 157RTA22200021F.d.09.2.P.Seq M00054742C:B12 211 158RTA22200021F.g.18.3.P.Seq M00054769A:E05 212 159RTA22200021F.h.15.3.P.Seq M00054777D:E09 213 160RTA22200021F.i.23.3.P.Seq M00054806B:G03 214 161RTA22200022F.d.04.1.P.Seq M00054893C:D03 215 162RTA22200022F.m.09.1.P.Seq M00054971D:D07 217 195RTA22200024F.i.11.1.P.Seq M00055209C:B07 218 164RTA22200024F.p.03.1.P.Seq M00055258B:D12 220 65RTA22200026F.d.17.1.P.Seq M00055423A:C07 222 124RTA22200231F.b.20.1.P.Seq M00007935D:A05 223 126RTA22200231F.l.22.1.P.Seq M00007985A:B08 224 132RTA22200232F.d.23.1.P.Seq M00021956B:A09 225 291RTA22200232F.m.17.1.P.Seq M00022140A:E11 226 142RTA22200241F.e.15.1.P.Seq M00026888A:A03 227 144RTA22200241F.g.22.1.P.Seq M00026903D:D11 228 115 X2.ga43_378506M00003852B:C01 230 255 gb|AA024920.1|AA024920 RG:364972:10009:B06 231262 gb|AA033519.1|AA033519 RG:471154:10009:H04 232 256gb|AA039790.1|AA039790 RG:376554:10009:B12 233 263gb|AA043829.1|AA043829 RG:487171:10009:H09 234 265gb|AA070046.1|AA070046 RG:530002:10002:A08 235 264gb|AA128438.1|AA128438 RG:526536:10002:A02 236 266gb|AA179757.1|AA179757 RG:612874:10002:G02 239 269gb|AA232253.1|AA232253 RG:666323:10010:B07 240 270gb|AA234451.1|AA234451 RG:669110:10010:B12 242 273gb|AA399596.1|AA399596 RG:729913:10010:G11 243 276gb|AA400338.1|AA400338 RG:742764:10011:A06 247 236gb|AA431134.1|AA431134 RG:781507:10011:E01 248 277gb|AA446295.1|AA446295 RG:781028:10011:D08 249 278gb|AA448898.1|AA448898 RG:785368:10011:E11 250 278gb|AA449542.1|AA449542 RG:785846:10011:F02 252 274gb|AA477696.1|AA477696 RG:740831:10010:H12 253 280gb|AA530983.1|AA530983 RG:985973:10012:B09 254 259gb|AA679027.1|AA679027 RG:432960:10009:E11 255 210gb|AA723679.1|AA723679 RG:1325847:10012:H07 256 213gb|AA829074.1|AA829074 RG:1374447:20004:G01 257 212gb|AA830348.1|AA830348 RG:1353123:10013:A06 258 214gb|AA885302.1|AA885302 RG:1461567:10013:E03 260 216gb|AA926951.1|AA926951 RG:1552386:10013:G04 262 219gb|AI004332.1|AI004332 RG:1631867:10014:B06 263 252gb|AI015644.1|AI015644 RG:1635546:10014:B08 264 220gb|AI017336.1|AI017336 RG:1638979:10014:C04 265 218gb|AI018495.1|AI018495 RG:1630930:10014:B05 266 221gb|AI031810.1|AI031810 RG:1645945:10014:D05 267 226gb|AI054129.1|AI054129 RG:1861510:20001:B03 268 212gb|AI066521.1|AI066521 RG:1637619:10014:C02 269 223gb|AI076187.1|AI076187 RG:1674098:10014:H01 270 221gb|AI079570.1|AI079570 RG:1674393:10014:H02 271 206gb|AI123832.1|AI123832 RG:1651303:10014:E01 272 225gb|AI207972.1|AI207972 RG:1838677:10015:E10 273 231gb|AI224731.1|AI224731 RG:2002384:20003:E01 274 233gb|AI265824.1|AI265824 RG:2006592:20003:F12 275 232gb|AI279390.1|AI279390 RG:2006302:20003:F08 276 227gb|AI298668.1|AI298668 RG:1895716:10015:G09 277 229gb|AI305997.1|AI305997 RG:1996788:20003:C10 278 230gb|AI306323.1|AI306323 RG:1996901:20003:D01 279 239gb|AI335279.1|AI335279 RG:2055807:10016:B09 280 238gb|AI336511.1|AI336511 RG:2051667:20003:H05 281 228gb|AI347995.1|AI347995 RG:1927470:10015:H08 282 235gb|AI356632.1|AI356632 RG:2012168:10016:B05 283 237gb|AI375104.1|AI375104 RG:2048081:10016:B08 284 241gb|AI421409.1|AI421409 RG:2097257:10016:C07 285 242gb|AI421521.1|AI421521 RG:2097294:10016:C08 286 243gb|AI523571.1|AI523571 RG:2117694:10016:E01 287 258 gb|H00135.1|H00135RG:43296:10005:C03 288 261 gb|H08424.1|H08424 RG:45623:10005:D09 289 260gb|H12948.1|H12948 RG:43534:10005:C04 290 236 gb|H54104.1|H54104RG:203031:10007:A09 293 246 gb|N55598.1|N55598 RG:244601:10007:E02 294245 gb|N75655.1|N75655 RG:244132:10007:E01 295 248 gb|N98702.1|N98702RG:278409:10008:B10 296 129 gb|R12138.1|R12138 RG:25258:10004:D09 298 2gb|R17980.1|R17980 RG:32281:10004:G05 299 254 gb|R21293.1|R21293RG:35892:10004:H10 300 249 gb|R41558.1|R41558 RG:29739:10004:F02 301 2gb|R56713.1|R56713 RG:41097:10005:B10 302 224 gb|R85309.1|R85309RG:180296:10006:G03 303 222 gb|R87679.1|R87679 RG:166410:10006:F01 304208 gb|T83145.1|T83145 RG:110764:10005:H04 305 250 gb|W16960.1|W16960RG:301608:10008:D09 306 251 gb|W24201.1|W24201 RG:306813:10008:E12 307252 gb|W45587.1|W45587 RG:323425:10008:F11 308 253 gb|W69496.1|W69496RG:343821:10008:H05 309 257 gb|W87460.1|W87460 RG:417109:10009:D09

Summary of Blast Search Results

Table 3 provides the results of BLASTN searches of the Genbank databaseusing the sequences of the polynucleotides as described above. Table 3includes 1) the SEQ ID NO; 2) the “CID” or Candidate IdentificationNumber to which the sequence is assigned; 3) the GenBank accessionnumber of the Blast hit; 4) a description of the gene encoded by theBlast hit (“HitDesc”) having the closest sequence homology to thesequence on the array (and in some instances contains a sequenceidentical to the sequence on the array); 5) the Blast score (“Score”),which value is obtained by adding the similarities and differences of analignment between the sequence and a database sequence, wherein a“match” is a positive value and a “mismatch” or “non-match” is anegative value; 6) the “Length” of the sequence, which represents thenumber of nucleotides in the database “hit”; 7) the Expect value (E)which describes the number of hits or matches “expected” if the databasewas random sequence, i.e. the E value describes the random backgroundnoise that exists for matches between sequences; and 8) the “Identities”ratio which is a ratio of number of bases in the query sequence thatexactly match the number of bases in the database sequence when aligned.

TABLE 3 SEQ GenBank ID Accession NO CID No. HitDesc Score Length ExpectIdentities 1 114 D29958 gi|473948|dbj|D29958.1|HUMORFA10 573 1011 1E−162289/289 Human mRNA for KIAA0116 gene, partial cds 2 123 NM_020510gi|10048405|ref|NM_020510.1|Mus 77.8 2112 3E−12 39/39 musculus frizzledhomolog 10 (Drosophila) (Fzd10), mRNA 3 114 D29958gi|473948|dbj|D29958.1|HUMORFA10 969 1011 0 559/575 Human mRNA forKIAA0116 gene, partial cds 4 1 XM_001344gi|11421753|ref|XM_001344.1|Homo 464 512 1E−129 234/234 sapiens S100calcium-binding protein A4 (calcium protein, calvasculin, metastasin,murine placental homolog) (S100A4), mRNA 5 2 NM_004443gi|4758287|ref|NM_004443.1|Homo 194 3805 3E−48 137/145 sapiens EphB3(EPHB3) mRNA 6 3 BC001014 gi|12654380|gb|BC001014.1|BC001014 444 13781E−123 224/224 Homo sapiens, Similar to methylenetetrahydrofolatedehydrogenase (NADP+ dependent), methenyltetrahydrofolatecyclohydrolase, formyltetrahydrofolate synthetase, clone IMAGE: 3344724,mRNA, partial cds 7 4 NM_001363 gi|4503336|ref|NM_001363.1|Homo 513 24221E−144 259/259 sapiens dyskeratosis congenita 1, dyskerin (DKC1), mRNA 85 NM_001699 gi|11863124|ref|NM_001699.2|Homo 543 4986 1E−153 281/282sapiens AXL receptor tyrosine kinase (AXL), transcript variant 2, mRNA 96 NM_001827 gi|4502858|ref|NM_001827.1|Homo 535 627 1E−150 279/282sapiens CDC28 protein kinase 2 (CKS2), mRNA 10 7 XM_011126gi|12730374|ref|XM_011126.1|Homo 515 2219 1E−144 260/260 sapiensArg/Abl-interacting protein ArgBP2 (ARGBP2), mRNA 11 8 BC002718gi|12803760|gb|BC002718.1|BC002718 299 1028 1E−79 223/236 Homo sapiens,type I transmembrane protein Fn14, clone MGC: 3386, mRNA, complete cds12 9 XM_007891 gi|11430799|ref|XM_007891.1|Homo 317 3171 3E−85 160/160sapiens cadherin 3, type 1, P-cadherin (placental) (CDH3), mRNA 13 10BC001883 gi|12804870|gb|BC001883.1|BC001883 490 2464 1E−137 255/259 Homosapiens, nucleolar phosphoprotein p130, clone MGC: 1494, mRNA, completecds 14 11 XM_002532 gi|11429973|ref|XM_002532.1|Homo 440 1132 1E−122244/255 sapiens 26S proteasome-associated pad1 homolog (POH1), mRNA 1512 BC005334 gi|13529121|gb|BC005334.1|BC005334 494 1047 1E−138 258/260Homo sapiens, centrin, EF-hand protein, 2, clone MGC: 12421, mRNA,complete cds 16 13 XM_009001 gi|12742166|ref|XM_009001.2|Homo 462 15061E−128 233/233 sapiens kallikrein 6 (neurosin, zyme) (KLK6), mRNA 17 14XM_005818 gi|12735488|ref|XM_005818.2|Homo 373 2420 1E−102 188/188sapiens arachidonate 5-lipoxygenase (ALOX5), mRNA 18 15 XM_012273gi|12737900|ref|XM_012273.1|Homo 396 3314 1E−109 200/200 sapiensforkhead box M1 (FOXM1), mRNA 19 167 AK000140gi|7020034|dbj|AK000140.1|AK000140 1114 1403 0 587/596 Homo sapiens cDNAFLJ20133 fis, clone COL06539 20 16 BC003146gi|13111946|gb|BC003146.1|BC003146 432 1720 1E−119 218/218 Homo sapiens,splicing factor 3b, subunit 3, 130 kD, clone MGC: 3924, mRNA, completecds 21 17 BC001763 gi|12804676|gb|BC001763.1|BC001763 404 1917 1E−111206/207 Homo sapiens, Similar to translocase of outer mitochondrialmembrane 34, clone MGC: 1252, mRNA, complete cds 22 18 XM_007326gi|11434291|ref|XM_007326.1|Homo 404 1944 1E−111 204/204 sapiens bonemorphogenetic protein 4 (BMP4), mRNA 23 19 XM_005376gi|12734932|ref|XM_005376.2|Homo 371 1503 1E−101 192/194 sapiensFriedreich ataxia (FRDA), mRNA 24 20 XM_010945gi|12729201|ref|XM_010945.1|Homo 452 614 1E−125 228/228 sapienshypothetical gene supported by XM_010945 (LOC65371), mRNA 25 21 AK018953gi|12858931|dbj|AK018953.1|AK018953 174 1297 5E−42 174/203 Mus musculusadult male testis cDNA, RIKEN full-length enriched library, clone:1700111D04, full insert sequence 26 22 BC003635gi|13177711|gb|BC003635.1|BC003635 456 1140 1E−127 230/230 Homo sapiens,matrix metalloproteinase 7 (matrilysin, uterine), clone MGC: 3913, mRNA,complete cds 27 23 XM_008589 gi|11427373|ref|XM_008589.1|Homo 440 17901E−122 224/225 sapiens pyrroline-5-carboxylate reductase 1 (PYCR1), mRNA28 24 BC001880 gi|12804864|gb|BC001880.1|BC001880 379 1469 1E−103191/191 Homo sapiens, Similar to insulin induced gene 1, clone MGC:1405, mRNA, complete cds 29 25 XM_003047gi|12729625|ref|XM_003047.2|Homo 353 3383 7E−96 178/178 sapiensminichromosome maintenance deficient (S. cerevisiae) 2 (mitotin) (MCM2),mRNA 30 26 NC_002548 gi|10314009|ref|NC_002548.1|Acute bee 38.2 94910.68 19/19 paralysis virus, complete genome 31 170 NM_004219gi|11038651|ref|NM_004219.2|Homo 1314 728 0 667/669 sapiens pituitarytumor-transforming 1 (PTTG1), mRNA 32 27 BC002479gi|12803322|gb|BC002479.1|BC002479 613 1479 1E−174 309/309 Homo sapiens,cathepsin H, clone MGC: 1519, mRNA, complete cds 33 28 BC000123gi|12652744|gb|BC000123.1|BC000123 545 1331 1E−153 275/275 Homo sapiens,pyridoxal (pyridoxine, vitamin B6) kinase, clone MGC: 3128, mRNA,complete cds 34 29 AK000836 gi|7021154|dbj|AK000836.1|AK000836 406 17031E−112 205/205 Homo sapiens cDNA FLJ20829 fis, clone ADKA03163, highlysimilar to D26488 Human mRNA for KIAA0007 gene 35 30 BC001425gi|12655140|gb|BC001425.1|BC001425 504 2499 1E−141 256/257 Homo sapiens,Similar to differential display and activated by p53, clone MGC: 1780,mRNA, complete cds 36 31 BC005301 gi|13529028|gb|BC005301.1|BC005301 442998 1E−122 225/226 Homo sapiens, integrin beta 3 binding protein(beta3-endonexin), clone MGC: 12370, mRNA, complete cds 37 32 Z27409gi|482916|emb|Z27409.1|HSRTKEPH 529 2398 1E−149 276/278 H. sapiens mRNAfor receptor tyrosine kinase eph (partial) 38 33 XM_003107gi|12729732|ref|XM_003107.2|Homo 436 1985 1E−120 227/228 sapienstransketolase (Wernicke- Korsakoff syndrome) (TKT), mRNA 39 34 AB002297gi|2224538|dbj|AB002297.1|AB002297 387 8063 1E−106 208/211 Human mRNAfor KIAA0299 gene, partial cds 40 35 XM_002591gi|12728749|ref|XM_002591.2|Homo 502 4732 1E−140 253/253 sapiensKIAA0173 gene product (KIAA0173), mRNA 41 36 XM_009101gi|11425196|ref|XM_009101.1|Homo 523 3374 1E−147 271/272 sapiensfucosyltransferase 1 (galactoside 2-alpha-L-fucosyltransferase, Bombayphenotype included) (FUT1), mRNA 42 37 AF082858gi|4587463|gb|AF082858.1|AF082858 494 829 1E−138 249/249 Homo sapienspterin carbinolamine dehydratase (PCD) mRNA, complete cds 43 38 BC001600gi|12804396|gb|BC001600.1|BC001600 533 1316 1E−150 269/269 Homo sapiens,D123 gene product, clone MGC: 1935, mRNA, complete cds 44 39 BC000871gi|12654114|gb|BC000871.1|BC000871 609 1489 1E−172 307/307 Homo sapiens,annexin A3, clone MGC: 5043, mRNA, complete cds 45 41 AL136600gi|13276700|emb|AL136600.1|HSM8015 504 1552 1E−141 254/254 74 Homosapiens mRNA; cDNA DKFZp564I1216 (from clone DKFZp564I1216); completecds 46 42 AK024772 gi|10437149|dbj|AK024772.1|AK024772 484 864 1E−135246/247 Homo sapiens cDNA: FLJ21119 fis, clone CAS05644, highly similarto HSA272196 Homo sapiens mRNA for hypothetical protein 47 43 BC004246gi|13279007|gb|BC004246.1|BC004246 438 4249 1E−121 221/221 Homo sapiens,mutS (E. coli) homolog 6, clone MGC: 10498, mRNA, complete cds 48 44X92474 gi|1045056|emb|X92474.1|HSCHTOG 238 6449 2E−61 122/123 H. sapiensmRNA for ch-TOG protein 49 45 BC002994gi|12804270|gb|BC002994.1|BC002994 476 2238 1E−132 246/248 Homo sapiens,clone MGC: 3823, mRNA, complete cds 50 46 AK025062gi|10437501|dbj|AK025062.1|AK025062 327 2692 4E−88 174/176 Homo sapienscDNA: FLJ21409 fis, clone COL03924 51 47 AP001247gi|10121151|dbj|AP001247.3|AP001247 36.2 16950 2.8 20/21 Homo sapiensgenomic DNA, chromosome 2p11.2, clone: lambda316 52 48 AF131838gi|4406677|gb|AF131838.1|AF131838 498 1462 1E−139 251/251 Homo sapiensclone 25107 mRNA sequence 53 49 XM_007647gi|11432476|ref|XM_007647.1|Homo 531 2111 1E−149 268/268 sapiensimmunoglobulin superfamily containing leucine-rich repeat (ISLR), mRNA54 50 AB048286 gi|13537296|dbj|AB048286.1|AB048286 476 2713 1E−132247/248 Homo sapiens GS1999full mRNA, complete cds 56 53 AK001515gi|7022818|dbj|AK001515.1|AK001515 333 884 6E−90 168/168 Homo sapienscDNA FLJ10653 fis, clone NT2RP2005890 57 54 AB023156gi|4589521|dbj|AB023156.1|AB023156 42.1 5537 0.055 24/25 Homo sapiensmRNA for KIAA0939 protein, partial cds 58 55 XM_008622gi|12740774|ref|XM_008622.2|Homo 507 1427 1E−142 256/256 sapiensthymidine kinase 1, soluble (TK1), mRNA 59 56 XM_003758gi|11416585|ref|XM_003758.1|Homo 422 2691 1E−116 215/216 sapienstransforming growth factor, beta- induced, 68 kD (TGFBI), mRNA 60 58XM_001732 gi|11423748|ref|XM_001732.1|Homo 500 2435 1E−140 252/252sapiens calcyclin binding protein (CACYBP), mRNA 61 59 BC001866gi|12804840|gb|BC001866.1|BC001866 396 2097 1E−109 239/256 Homo sapiens,replication factor C (activator 1) 5 (36.5 kD), clone MGC: 1155, mRNA,complete cds 62 60 BC000293 gi|12653056|gb|BC000293.1|BC000293 87.7 7332E−16 58/65 Homo sapiens, non-metastatic cells 1, protein (NM23A)expressed in, clone MGC: 8334, mRNA, complete cds 63 63 XM_008043gi|12739769|ref|XM_008043.2|Homo 519 1739 1E−146 262/262 sapiensdipeptidase 1 (renal) (DPEP1), mRNA 64 64 AB052751gi|11967903|dbj|AB052751.1|AB052751 527 1863 1E−148 266/266 Homo sapiensAxin2 mRNA for conductin, partial cds and 3′UTR 65 65 BC005832gi|13543336|gb|BC005832.1|BC005832 460 1444 1E−128 232/232 Homo sapiens,KIAA0101 gene product, clone MGC: 2250, mRNA, complete cds 66 66XM_002190 gi|11428365|ref|XM_002190.1|Homo 472 3152 1E−131 238/238sapiens chromosome 1 open reading frame 2 (C1ORF2), mRNA 67 67 XM_010360gi|12743462|ref|XM_010360.2|Homo 505 3746 1E−141 255/255 sapienstranscription factor NRF (NRF), mRNA 68 68 AL122064gi|6102857|emb|AL122064.1|HSM801208 502 1320 1E−140 257/259 Homo sapiensmRNA; cDNA DKFZp434M231 (from clone DKFZp434M231); partial cds 70 71XM_005226 gi|11425871|ref|XM_005226.1|Homo 507 2619 1E−142 256/256sapiens antizyme inhibitor (LOC51582), mRNA 71 74 BC002956gi|12804196|gb|BC002956.1|BC002956 484 1185 1E−135 244/244 Homo sapiens,ClpP (caseinolytic protease, ATP-dependent, proteolytic subunit, E.coli) homolog, clone MGC: 1379, mRNA, complete cds 73 100 NM_014791gi|7661973|ref|NM_014791.1|Homo 1211 2470 0 691/708 sapiens KIAA0175gene product (KIAA0175), mRNA 74 105 BC005864gi|13543414|gb|BC005864.1|BC005864 1108 1430 0 621/635 Homo sapiens,cyclin-dependent kinase 4, clone MGC: 3719, mRNA, complete cds 75 106XM_005404 gi|11428250|ref|XM_005404.1|Homo 1203 2446 0 631/638 sapienscatenin (cadherin-associated protein), alpha-like 1 (CTNNAL1), mRNA 76104 BC002362 gi|12803116|gb|BC002362.1|BC002362 1269 1318 0 643/644 Homosapiens, lactate dehydrogenase B, clone MGC: 8627, mRNA, complete cds 7775 AF065389 gi|3152702|gb|AF065389.1|AF065389 434 1405 1E−120 236/244Homo sapiens tetraspan NET-4 mRNA, complete cds 78 76 BC004863gi|13436073|gb|BC004863.1|BC004863 587 2229 1E−166 303/304 Homo sapiens,Similar to phosphoserine aminotransferase, clone MGC: 10519, mRNA,complete cds 79 77 XM_011917 gi|12735709|ref|XM_011917.1|Homo 509 14141E−143 259/260 sapiens adenosine kinase (ADK), mRNA 80 78 BC000897gi|12654158|gb|BC000897.1|BC000897 143 683 8E−33 102/107 Homo sapiens,interferon induced transmembrane protein 1 (9-27), clone MGC: 5195,mRNA, complete cds 81 79 NM_014641 gi|7661965|ref|NM_014641.1|Homo 3356940 3E−90 196/206 sapiens KIAA0170 gene product (KIAA0170), mRNA 82 80XM_012967 gi|12742527|ref|XM_012967.1|Homo 430 1188 1E−119 231/233sapiens RAE1 (RNA export 1, S. pombe) homolog (RAE1), mRNA 83 81XM_003913 gi|12719136|ref|XM_003913.2|Homo 571 5348 1E−161 288/288sapiens integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor)(ITGA2), mRNA 84 109 AK024039 gi|10436304|dbj|AK024039.1|AK024039 4222224 1E−116 377/443 Homo sapiens cDNA FLJ13977 fis, clone Y79AA1001603,weakly similar to POLYPEPTIDE N- ACETYLGALACTOSAMINYLTRANSFERASE (EC2.4.1.41) 85 110 XM_009492 gi|11420665|ref|XM_009492.1|Homo 852 2627 0440/444 sapiens v-myb avian myeloblastosis viral oncogene homolog-like 2(MYBL2), mRNA 86 111 XM_009587 gi|12742401|ref|XM_009587.2|Homo 749 21080 392/394 sapiens TH1 drosophila homolog (HSPC130), mRNA 87 121NM_001408 gi|13325063|ref|NM_001408.1|Homo 1067 10531 0 627/660 sapienscadherin, EGF LAG seven-pass G-type receptor 2, flamingo (Drosophila)homolog (CELSR2), mRNA 88 118 AF226998gi|12655885|gb|AF226998.1|AF226998 775 734 0 391/391 Homo sapiensdpy-30-like protein mRNA, complete cds 89 41 BC001106gi|12654544|gb|BC001106.1|BC001106 416 1542 1E−114 214/216 Homo sapiens,hypothetical protein, clone MGC: 891, mRNA, complete cds 90 139XM_009005 gi|11424670|ref|XM_009005.1|Homo 1112 1186 0 617/630 sapienskallikrein 11 (KLK11), mRNA 91 83 XM_006067gi|12736004|ref|XM_006067.2|Homo 321 2525 4E−86 189/194 sapiens7-dehydrocholesterol reductase (DHCR7), mRNA 92 85 AF092569gi|3986473|gb|AF092569.1|HSEIFP1 87.7 299 2E−16 74/79 Homo sapienstranslation initiation factor eIF3 p40 subunit gene, exon 1 93 117BC004264 gi|13279061|gb|BC004264.1|BC004264 1021 3138 0 564/582 Homosapiens, Similar to EphB4, clone IMAGE: 3611312, mRNA, partial cds 94113 BC000277 gi|12802987|gb|BC000277.1|BC000277 1011 2947 0 586/618 Homosapiens, clone MGC: 1892, mRNA, complete cds 95 87 NM_015339gi|12229216|ref|NM_015339.1|Homo 599 4713 1E−169 302/302 sapiensactivity-dependent neuroproctective protein (ADNP), mRNA 96 88 XM_009845gi|11526339|ref|XM_009845.1|Homo 505 1291 1E−141 255/255 sapienscatechol-O-methyltransferase (COMT), mRNA 97 89 BC000509gi|12653474|gb|BC000509.1|BC000509 517 1008 1E−145 261/261 Homo sapiens,proteasome (prosome, macropain) subunit, beta type, 7, clone MGC: 8507,mRNA, complete cds 98 125 AK024618 gi|10436934|dbj|AK024618.1|AK0246181199 1804 0 662/676 Homo sapiens cDNA: FLJ20965 fis, clone ADSH01104 99128 D80001 gi|1136417|dbj|D80001.1|D80001 1138 4994 0 639/663 Human mRNAfor KIAA0179 gene, partial cds 100 127 BC004899gi|13436169|gb|BC004899.1|BC004899 930 1688 0 579/619 Homo sapiens,sigma receptor (SR31747 binding protein 1), clone MGC: 3851, mRNA,complete cds 101 129 BC003129 gi|13111916|gb|BC003129.1|BC003129 10431882 0 583/602 Homo sapiens, non-POU-domain- containing,octamer-binding, clone MGC: 3380, mRNA, complete cds 102 130 XM_009690gi|12742251|ref|XM_009690.2|Homo 438 2277 1E−121 367/404 sapienshypothetical protein FLJ10850 (FLJ10850), mRNA 104 136 XM_005908gi|11432093|ref|XM_005908.1|Homo 1235 2237 0 642/646 sapienshypothetical protein FLJ10540 (FLJ10540), mRNA 106 5 NM_001699gi|11863124|ref|NM_001699.2|Homo 922 4986 0 550/572 sapiens AXL receptortyrosine kinase (AXL), transcript variant 2, mRNA 107 137 NM_025927gi|13385417|ref|NM_025927.1|Mus 228 1486 1E−57 223/259 musculus RIKENcDNA 2600005P05 gene (2600005P05Rik), mRNA 108 138 AK023154gi|10434948|dbj|AK023154.1|AK023154 924 3040 0 524/541 Homo sapiens cDNAFLJ13092 fis, clone NT2RP3002147 109 141 AB017710gi|5821114|dbj|AB017710.1|AB017710 1067 2353 0 570/582 Homo sapiensU50HG genes for U50′ snoRNA and U50 snoRNA, complete sequence 110 90NM_011775 gi|6756080|ref|NM_011775.1|Mus 40.1 2185 0.21 20/20 musculuszona pellucida glycoprotein 2 (Zp2), mRNA 111 145 AF086315gi|3483660|gb|AF086315.1|HUMZD52F10 841 600 0 467/480 Homo sapiens fulllength insert cDNA clone ZD52F10 112 91 XM_002596gi|12728741|ref|XM_002596.2|Homo 361 2877 4E−98 201/209 sapiens proteintyrosine phosphatase, receptor type, N (PTPRN), mRNA 113 92 XM_004484gi|11418942|ref|XM_004484.1|Homo 482 1325 1E−134 243/243 sapiens tumorprotein D52-like 1 (TPD52L1), mRNA 114 93 BC000331gi|12653128|gb|BC000331.1|BC000331 583 935 1E−165 305/310 Homo sapiens,proteasome (prosome, macropain) subunit, beta type, 4, clone MGC: 8522,mRNA, complete cds 116 100 NM_014791 gi|7661973|ref|NM_014791.1|Homo1185 2470 0 644/664 sapiens KIAA0175 gene product (KIAA0175), mRNA 118123 XM_004185 gi|12731991|ref|XM_004185.2|Homo 751 4092 0 463/481sapiens valyl-tRNA synthetase 2 (VARS2), mRNA 119 94 XM_004750gi|12733059|ref|XM_004750.2|Homo 484 629 1E−135 244/244 sapiens nudix(nucleoside diphosphate linked moiety X)-type motif 1 (NUDT1), mRNA 12095 XM_006928 gi|12737727|ref|XM_006928.2|Homo 412 4870 1E−113 239/248sapiens FOXJ2 forkhead factor (LOC55810), mRNA 121 96 AL133104gi|6453587|emb|AL133104.1|HSM801384 601 1186 1E−170 303/303 Homo sapiensmRNA; cDNA DKFZp434E1822 (from clone DKFZp434E1822); partial cds 122 98BC004528 gi|13528647|gb|BC004528.1|BC004528 466 2751 1E−129 244/246 Homosapiens, clone MGC: 3017, mRNA, complete cds 123 103 AF097514gi|4808600|gb|AF097514.1|AF097514 1302 5221 0 721/738 Homo sapiensstearoyl-CoA desaturase (SCD) mRNA, complete cds 124 103 AF097514gi|4808600|gb|AF097514.1|AF097514 1328 5221 0 720/734 Homo sapiensstearoyl-CoA desaturase (SCD) mRNA, complete cds 125 133 AF220656gi|7107358|gb|AF220656.1|AF220656 936 3227 0 529/539 Homo sapiensapoptosis-associated nuclear protein PHLDA1 (PHLDA1) mRNA, partial cds126 133 AF220656 gi|7107358|gb|AF220656.1|AF220656 969 3227 0 544/555Homo sapiens apoptosis-associated nuclear protein PHLDA1 (PHLDA1) mRNA,partial cds 130 115 AF019770 gi|2674084|gb|AF019770.1|AF019770 1277 12020 735/751 Homo sapiens macrophage inhibitory cytokine-1 (MIC-1) mRNA,complete cds 131 106 AK022926 gi|10434597|dbj|AK022926.1|AK022926 5892455 1E−166 299/300 Homo sapiens cDNA FLJ12864 fis, clone NT2RP2003604,highly similar to Homo sapiens alpha-catenin-like protein (CTNNAL1) mRNA132 113 BC000277 gi|12802987|gb|BC000277.1|BC000277 513 2947 1E−144262/263 Homo sapiens, clone MGC: 1892, mRNA, complete cds 133 113XM_006213 gi|12736410|ref|XM_006213.2|Homo 579 6477 1E−163 299/300sapiens KIAA0712 gene product (KIAA0712), mRNA 134 106 XM_005404gi|11428250|ref|XM_005404.1|Homo 561 2446 1E−158 300/306 sapiens catenin(cadherin-associated protein), alpha-like 1 (CTNNAL1), mRNA 135 116BC001068 gi|12654476|gb|BC001068.1|BC001068 595 2333 1E−168 300/300 Homosapiens, clone IMAGE: 2823731, mRNA, partial cds 136 117 BC004264gi|13279061|gb|BC004264.1|BC004264 486 3138 1E−135 250/252 Homo sapiens,Similar to EphB4, clone IMAGE: 3611312, mRNA, partial cds 138 123 Y09668gi|1834428|emb|Y09668.1|DRTKLELF1 36.2 2272 3.5 18/18 D. rerio mRNA fortyrosine kinase ligand (elf-1) 140 140 XM_008802gi|12741169|ref|XM_008802.2|Homo 710 3185 0 358/358 sapiensretinoblastoma-binding protein 8 (RBBP8), mRNA 141 143 XM_009111gi|12741675|ref|XM_009111.2|Homo 672 1453 0 362/367 sapienssulfotransferase family, cytosolic, 2B, member 1 (SULT2B1), mRNA 142 121NM_001408 gi|13325063|ref|NM_001408.1|Homo 755 10531 0 388/389 sapienscadherin, EGF LAG seven-pass G-type receptor 2, flamingo (Drosophila)homolog (CELSR2), mRNA 143 121 NM_001408gi|13325063|ref|NM_001408.1|Homo 741 10531 0 376/377 sapiens cadherin,EGF LAG seven-pass G-type receptor 2, flamingo (Drosophila) homolog(CELSR2), mRNA 144 139 XM_009005 gi|11424670|ref|XM_009005.1|Homo 6221186 1E−176 340/346 sapiens kallikrein 11 (KLK11), mRNA 145 112XM_003733 gi|12731080|ref|XM_003733.2|Homo 753 2088 0 380/380 sapiensDEAD-box protein abstrakt (ABS), mRNA 147 166 AF216754gi|6707650|gb|AF216754.1|AF216754 567 354 1E−160 296/298 Homo sapiensover-expressed breast tumor protein (OBTP) mRNA, complete cds 148 167XM_003384 gi|12730453|ref|XM_003384.2|Homo 640 748 0 323/323 sapienshypothetical protein (LOC51316), mRNA 149 169 XM_009527gi|11420875|ref|XM_009527.1|Homo 751 594 0 382/383 sapiens secretoryleukocyte protease inhibitor (antileukoproteinase) (SLPI), mRNA 150 30AF279897 gi|12751120|gb|AF279897.1|AF279897 654 727 0 333/334 Homosapiens PNAS-143 mRNA, complete cds 151 170 NM_004219gi|11038651|ref|NM_004219.2|Homo 730 728 0 368/368 sapiens pituitarytumor-transforming 1 (PTTG1), mRNA 152 171 S76771gi|914225|gb|S76771.1|S76771 210 6849 1E−52 168/185 TPO = thrombopoietin[human, Genomic, 6849 nt] 153 171 M81890 gi|186274|gb|M81890.1|HUMIL11A216 6870 2E−54 180/203 Human interleukin 11 (IL11) gene, complete mRNA154 172 XM_004952 gi|12733392|ref|XM_004952.2|Homo 603 2861 1E−171310/312 sapiens solute carrier family 26, member 3 (SLC26A3), mRNA 155147 XM_009488 gi|12742285|ref|XM_009488.2|Homo 716 770 0 361/361 sapiensubiquitin carrier protein E2-C (UBCH10), mRNA 156 149 XM_011755gi|12734624|ref|XM_011755.1|Homo 733 2566 0 370/370 sapiens SETtranslocation (myeloid leukemia-associated) (SET), mRNA 157 150 L19183gi|307154|gb|L19183.1|HUMMAC30X 593 2002 1E−168 323/331 Human MAC30mRNA, 3′ end 158 151 AK024303 gi|10436651|dbj|AK024303.1|AK024303 6981591 0 352/352 Homo sapiens cDNA FLJ14241 fis, clone OVARC1000533 159173 BC001410 gi|12655116|gb|BC001410.1|BC001410 682 577 0 354/356 Homosapiens, S100 calcium-binding protein A11 (calgizzarin), clone MGC:2149, mRNA, complete cds 161 175 BC001308gi|12654922|gb|BC001308.1|BC001308 646 2263 0 353/362 Homo sapiens,clone HQ0310 PRO0310p1, clone MGC: 5505, mRNA, complete cds 162 176XM_009004 gi|12742171|ref|XM_009004.2|Homo 458 1448 1E−127 231/231sapiens kallikrein 10 (KLK10), mRNA 163 177 XM_006705gi|12737366|ref|XM_006705.2|Homo 630 784 1E−179 324/326 sapiensnascent-polypeptide-associated complex alpha polypeptide (NACA), mRNA164 178 AF102848 gi|12641918|gb|AF102848.1|AF102848 739 1649 0 379/381Homo sapiens keratin 23 (KRT23) mRNA, complete cds 165 179 XM_003512gi|12730699|ref|XM_003512.2|Homo 718 1231 0 371/374 sapiens amphiregulin(schwannoma- derived growth factor) (AREG), mRNA 166 180 XM_005313gi|12734542|ref|XM_005313.2|Homo 652 1275 0 335/337 sapiensgamma-glutamyl hydrolase (conjugase, folylpolygammaglutamyl hydrolase)(GGH), mRNA 168 182 XM_010117 gi|11419764|ref|XM_010117.1|Homo 690 25190 360/364 sapiens plastin 3 (T isoform) (PLS3), mRNA 169 183 L47277gi|986911|gb|L47277.1|HUMTOPATRA 646 994 0 353/362 Homo sapiens (cellline HepG2, HeLa) alpha topoisomerase truncated-form mRNA, 3′UTR 170 184XM_012941 gi|12742342|ref|XM_012941.1|Homo 670 3071 0 341/342 sapienschromosome 20 open reading frame 1 (C20ORF1), mRNA 171 185 NM_000581gi|10834975|ref|NM_000581.1|Homo 640 1134 0 339/343 sapiens glutathioneperoxidase 1 (GPX1), mRNA 172 185 NM_000581gi|10834975|ref|NM_000581.1|Homo 640 1134 0 338/343 sapiens glutathioneperoxidase 1 (GPX1), mRNA 173 186 X06705 gi|35511|emb|X06705.1|HSPLAX700 883 0 353/353 Human PLA-X mRNA 174 187 D45915gi|1483130|dbj|D45915.1|D45915 666 2584 0 336/336 Human mRNA for p80protein, complete cds 176 189 BC000242gi|12652962|gb|BC000242.1|BC000242 521 849 1E−146 280/286 Homo sapiens,CGI-138 protein, clone MGC: 676, mRNA, complete cds 177 190 BC005945gi|13543585|gb|BC005945.1|BC005945 567 1391 1E−160 295/298 Homo sapiens,MAD2 (mitotic arrest deficient, yeast, homolog)-like 1, clone MGC:14577, mRNA, complete cds 179 192 XM_010835gi|12728550|ref|XM_010835.1|Homo 452 1679 1E−125 313/340 sapiens similarto hypothetical protein (H. sapiens) (LOC65349), mRNA 180 193 XM_009475gi|11420562|ref|XM_009475.1|Homo 668 2110 0 340/341 sapiensS-adenosylhomocysteine hydrolase (AHCY), mRNA 181 194 AF054183gi|4092053|gb|AF054183.1|AF054183 690 1148 0 351/352 Homo sapiens GTPbinding protein mRNA, complete cds 182 195 BC005356gi|13529175|gb|BC005356.1|BC005356 396 1050 1E−108 200/200 Homo sapiens,Similar to hypothetical protein MGC3077, clone MGC: 12457, mRNA,complete cds 183 196 XM_006545 gi|12736918|ref|XM_006545.2|Homo 613 5881E−173 309/309 sapiens hypothetical protein (HSPC152), mRNA 184 197XM_003598 gi|12730828|ref|XM_003598.2|Homo 662 440 0 345/349 sapiensS100 calcium-binding protein P (S100P), mRNA 185 197 NM_005980gi|5174662|ref|NM_005980.1|Homo 565 439 1E−159 291/293 sapiens S100calcium-binding protein P (S100P), mRNA 190 199 M80340gi|339767|gb|M80340.1|HUMTNL12 539 6075 1E−151 351/377 Human transposonL1.1 with a base deletion relative to L1.2B resulting in a prematurestop codon in the coding region 191 199 U93574gi|2072975|gb|U93574.1|HSU93574 404 5979 1E−111 290/318 Human L1 elementL1.39 p40 and putative p150 genes, complete cds 192 200 AC002143gi|2168303|gb|AC002143.1|AC002143 214 4025 8E−54 235/275 Homo sapiens(subclone 4_b10 from BAC H102) DNA sequence, complete sequence 193 176BC002710 gi|12803744|gb|BC002710.1|BC002710 648 1542 0 327/327 Homosapiens, kallikrein 10, clone MGC: 3667, mRNA, complete cds 194 201XM_004286 gi|11418526|ref|XM_004286.1|Homo 561 700 1E−158 289/291sapiens ribosomal protein L10a (RPL10A), mRNA 196 118 AF226998gi|12655885|gb|AF226998.1|AF226998 505 734 1E−141 255/255 Homo sapiensdpy-30-like protein mRNA, complete cds 198 204 AL3900221gi|10862787|emb|AL390022.11|AL390022 470 9277 1E−130 337/369 Human DNAsequence from clone RP11-370B6 on chromosome X, complete sequence [Homosapiens] 200 206 BC002476 gi|12803316|gb|BC002476.1|BC002476 615 6951E−174 316/318 Homo sapiens, non-metastatic cells 2, protein (NM23B)expressed in, clone MGC: 2212, mRNA, complete cds 201 207 XM_005235gi|12734360|ref|XM_005235.2|Homo 605 1507 1E−171 311/313 sapienseukaryotic translation initiation factor 3, subunit 6 (48 kD) (EIF3S6),mRNA 202 152 BC004427 gi|13325215|gb|BC004427.1|BC004427 611 967 1E−173321/324 Homo sapiens, proteasome (prosome, macropain) subunit, alphatype, 7, clone MGC: 3755, mRNA, complete cds 204 151 AK024303gi|10436651|dbj|AK024303.1|AK024303 585 1591 1E−165 295/295 Homo sapienscDNA FLJ14241 fis, clone OVARC1000533 205 151 AK024303gi|10436651|dbj|AK024303.1|AK024303 591 1591 1E−167 298/298 Homo sapienscDNA FLJ14241 fis, clone OVARC1000533 206 153 XM_003927gi|11417090|ref|XM_003927.1|Homo 656 473 0 337/339 sapiens Apg12(autophagy 12, S. cerevisiae)- like (APG12L), mRNA 207 154 BC000947gi|13111828|gb|BC000947.2|BC000947 644 1608 0 336/340 Homo sapiens,clone IMAGE: 3450586, mRNA, partial cds 208 155 XM_004478gi|12732587|ref|XM_004478.2|Homo 660 1993 0 339/341 sapiens glyoxalase I(GLO1), mRNA 209 156 L36587 gi|598241|gb|L36587.1|HUMUHGA 664 1357 0335/335 Homo sapiens spliced UHG RNA 210 157 BC000447gi|12653354|gb|BC000447.1|BC000447 656 585 0 334/335 Homo sapiens,macrophage migration inhibitory factor (glycosylation- inhibitingfactor), clone MGC: 8444, mRNA, complete cds 211 158 BC001708gi|12804576|gb|BC001708.1|BC001708 626 906 1E−178 319/320 Homo sapiens,ribosomal protein S3A, clone MGC: 1626, mRNA, complete cds 212 159BC005008 gi|13477106|gb|BC005008.1|BC005008 668 2249 0 337/337 Homosapiens, carcinoembryonic antigen-related cell adhesion molecule 6(non-specific cross reacting antigen), clone MGC: 10467, mRNA, completecds 213 160 AL110141 gi|5817036|emb|AL110141.1|HSM800785 519 656 1E−145265/266 Homo sapiens mRNA; cDNA DKFZp564D0164 (from clone DKFZp564D0164)214 161 NM_014366 gi|7657047|ref|NM_014366.1|Homo 634 2059 1E−180335/343 sapiens putative nucleotide binding protein, estradiol-induced(E2IG3), mRNA 215 162 AL359585 gi|8655645|emb|AL359585.1|HSM802687 1292183 4E−28 68/69 Homo sapiens mRNA; cDNA DKFZp762B195 (from cloneDKFZp762B195) 217 195 NM_024051 gi|13129017|ref|NM_024051.1|Homo 6461195 0 329/330 sapiens hypothetical protein MGC3077 (MGC3077), mRNA 218164 XM_006551 gi|11441541|ref|XM_006551.1|Homo 601 905 1E−170 321/327sapiens interferon induced transmembrane protein 2 (1-8D) (IFITM2), mRNA220 65 XM_007736 gi|11433251|ref|XM_007736.1|Homo 648 836 0 330/331sapiens KIAA0101 gene product (KIAA0101), mRNA 222 124 U07571gi|497170|gb|U07571.1|HSU07571 46.1 392 0.005 23/23 Human cloneS1X13-SS13A dinucleotide repeat at Xq21 223 126 AF288394gi|12620197|gb|AF288394.1|AF288394 718 1961 0 377/382 Homo sapiensC1orf19 mRNA, partial cds 224 132 U35622 gi|5733846|gb|U35622.2|HSU35622779 2107 0 398/400 Homo sapiens EWS protein/E1A enhancer binding proteinchimera mRNA, complete cds 225 291 BC004928gi|13436256|gb|BC004928.1|BC004928 793 2567 0 400/400 Homo sapiens,clone MGC: 10493, mRNA, complete cds 226 142 AL137736gi|6808315|emb|AL137736.1|HSM802318 692 2053 0 363/365 Homo sapiensmRNA; cDNA DKFZp586P2321 (from clone DKFZp586P2321) 227 144 XM_008130gi|11424226|ref|XM_008130.1|Homo 785 1361 0 396/396 sapiensgalactokinase 1 (GALK1), mRNA 228 115 AF019770gi|2674084|gb|AF019770.1|AF019770 1370 1202 0 721/729 Homo sapiensmacrophage inhibitory cytokine-1 (MIC-1) mRNA, complete cds 230 255AF179710 gi|9836821|gb|AF179710.1|AF179710 40.1 1096 0.35 20/20 Pongopygmaeus RH50 glycoprotein (RHAG) gene, intron 9 231 262 XM_009943gi|11418022|ref|XM_009943.1|Homo 864 5486 0 455/462 sapiens tissueinhibitor of metalloproteinase 3 (Sorsby fundus dystrophy,pseudoinflammatory) (TIMP3), mRNA 232 256 AF134904gi|4809150|gb|AF134904.1|AF134904 42.1 2558 0.097 21/21 Schistocercagregaria semaphorin 2a mRNA, complete cds 233 263 BC003002gi|12804286|gb|BC003002.1|BC003002 523 2165 1E−147 284/294 Homo sapiens,polo (Drosophia)-like kinase, clone MGC: 3988, mRNA, complete cds 234265 M68513 gi|199119|gb|M68513.1|MUSMEK4 882 3197 0 491/503 Mouseeph-related receptor tyrosine kinase (Mek4) mRNA, complete cds 235 264XM_007931 gi|12739533|ref|XM_007931.2|Homo 730 1593 0 407/414 sapienssolute carrier family 9 (sodium/hydrogen exchanger), isoform 3regulatory factor 2 (SLC9A3R2), mRNA 236 266 XM_003748gi|12731108|ref|XM_003748.2|Homo 387 2967 1E−106 267/302 sapiensserum-inducible kinase (SNK), mRNA 239 269 BC001401gi|12655098|gb|BC001401.1|BC001401 773 1571 0 396/398 Homo sapiens,Similar to sterile-alpha motif and leucine zipper containing kinase AZK,clone MGC: 808, mRNA, complete cds 240 270 S76617gi|914203|gb|S76617.1|S76617 38.2 2608 0.87 19/19 blk = protein tyrosinekinase [human, B lymphocytes, mRNA, 2608 nt] 242 273 AK006144gi|12839086|dbj|AK006144.1|AK006144 323 1387 1E−86 233/255 Mus musculusadult male testis cDNA, RIKEN full-length enriched library, clone:1700020B19, full insert sequence 243 276 X91656gi|2125862|emb|X91656.1|MMSRP20 494 13121 1E−138 262/265 M. musculusSrp20 gene 247 236 BC002499 gi|12803360|gb|BC002499.1|BC002499 640 21290 330/331 Homo sapiens, serine/threonine kinase 15, clone MGC: 1605,mRNA, complete cds 248 277 NM_003618 gi|4506376|ref|NM_003618.1|Homo 7024380 0 361/362 sapiens mitogen-activated protein kinase kinase kinasekinase 3 (MAP4K3), mRNA 249 278 NM_018492gi|8923876|ref|NM_018492.1|Homo 779 1548 0 400/401 sapiens PDZ-bindingkinase; T-cell originated protein kinase (TOPK), mRNA 250 278 XM_005110gi|12734111|ref|XM_005110.2|Homo 1003 1537 0 506/506 sapiens PDZ-bindingkinase; T-cell originated protein kinase (TOPK), mRNA 252 274 BC002466gi|12803300|gb|BC002466.1|BC002466 1074 2451 0 575/581 Homo sapiens,v-raf murine sarcoma 3611 viral oncogene homolog 1, clone MGC: 2356,mRNA, complete cds 253 280 XM_001729 gi|11423735|ref|XM_001729.1|Homo751 1658 0 385/387 sapiens v-akt murine thymoma viral oncogene homolog 3(protein kinase B, gamma) (AKT3), mRNA 254 259 NM_002893gi|13259504|ref|NM_002893.2|Homo 1164 1946 0 715/746 sapiensretinoblastoma-binding protein 7 (RBBP7), mRNA 255 210 AB056798gi|13365896|dbj|AB056798.1|AB056798 678 4521 0 435/461 Macacafascicularis brain cDNA clone: QflA-11110, full insert sequence 256 213AJ302649 gi|11140019|emb|AJ302649.1|DRE302649 42.1 2188 0.058 21/21Danio rerio mRNA for GABAA receptor betaZ2 subunit (gabaabeta2 gene) 257212 L27711 gi|808006|gb|L27711.1|HUMKAP1A 1057 844 0 550/553 Humanprotein phosphatase (KAP1) mRNA, complete cds 258 214 NM_004336gi|4757877|ref|NM_004336.1|Homo 1318 3446 0 694/701 sapiens buddinguninhibited by benzimidazoles 1 (yeast homolog) (BUB1), mRNA 260 216NM_004300 gi|4757713|ref|NM_004300.1|Homo 985 2222 0 621/656 sapiensacid phosphatase 1, soluble (ACP1), transcript variant a, mRNA 262 219AK026166 gi|10438929|dbj|AK026166.1|AK026166 1402 1813 0 838/871 Homosapiens cDNA: FLJ22513 fis, clone HRC12111, highly similar to HUMKUPHuman Ku (p70/p80) subunit mRNA 263 252 BC004937gi|13436283|gb|BC004937.1|BC004937 898 1032 0 475/480 Homo sapiens,clone MGC: 10779, mRNA, complete cds 264 220 XM_006375gi|12736706|ref|XM_006375.2|Homo 1316 737 0 693/703 sapiens glutathioneS-transferase pi (GSTP1), mRNA 265 218 BC001827gi|12804774|gb|BC001827.1|BC001827 1259 1073 0 672/683 Homo sapiens,Similar to deoxythymidylate kinase (thymidylate kinase), clone MGC:3923, mRNA, complete cds 266 221 BC002900gi|12804094|gb|BC002900.1|BC002900 1217 867 0 699/728 Homo sapiens,Similar to proteasome (prosome, macropain) subunit, alpha type, 2, cloneIMAGE: 3942625, mRNA, partial cds 267 226 AF064029gi|4091894|gb|AF064029.1|AF064029 60 779 0.0000002 30/30 Helianthustuberosus lectin 1 mRNA, complete cds 268 212 L27711gi|808006|gb|L27711.1|HUMKAP1A 1257 844 0 694/705 Human proteinphosphatase (KAP1) mRNA, complete cds 269 223 XM_011470gi|12732420|ref|XM_011470.1|Homo 1029 2591 0 519/519 sapiensmyristoylated alanine-rich protein kinase C substrate (MARCKS, 80K-L)(MACS), mRNA 270 221 BC002900 gi|12804094|gb|BC002900.1|BC002900 1330867 0 724/739 Homo sapiens, Similar to proteasome (prosome, macropain)subunit, alpha type, 2, clone IMAGE: 3942625, mRNA, partial cds 271 206BC002476 gi|12803316|gb|BC002476.1|BC002476 1203 695 0 610/611 Homosapiens, non-metastatic cells 2, protein (NM23B) expressed in, cloneMGC: 2212, mRNA, complete cds 272 225 XM_007980gi|12739602|ref|XM_007980.2|Homo 904 1866 0 481/487 sapiensmembrane-associated tyrosine- and threonine-specific cdc2-inhibitorykinase (PKMYT1), mRNA 273 231 S50810 gi|262070|gb|S50810.1|S50810{satellite 52 1086 0.00003 29/30 DNA} [Drosophila melanogaster, Docmobile element, Transposon, 1086 nt] 274 233 AF217396gi|8132773|gb|AF217396.1|AF217396 46.1 2007 0.004 23/23 Drosophilamelanogaster clone 2G2 unknown mRNA 275 232 L29057gi|609636|gb|L29057.1|XELCADH 40.1 4097 0.081 20/20 Xenopus laevis(clone: XTCAD-1) cadherin gene, complete cds 276 227 XM_008475gi|11426657|ref|XM_008475.1|Homo 40.1 6962 0.32 20/20 sapiens KIAA0100gene product (KIAA0100), mRNA 277 229 M34230gi|204651|gb|M34230.1|RATHPA1 Rat 56 3282 0.000002 28/28 haptoglobin(Hp) gene, exons 1, 2 and 3 278 230 AJ302649gi|11140019|emb|AJ302649.1|DRE302649 50.1 2188 0.0002 25/25 Danio reriomRNA for GABAA receptor betaZ2 subunit (gabaabeta2 gene) 279 239NM_021158 gi|11056039|ref|NM_021158.1|Homo 710 2257 0 358/358 sapiensprotein kinase domains containing protein similar to phosphoprotein C8FW(LOC57761), mRNA 280 238 AX030958 gi|10278361|emb|AX030958.1|AX030958 563828 0.000005 28/28 Sequence 7 from Patent WO9800549 281 228 XM_010102gi|11419709|ref|XM_010102.1|Homo 1469 1767 0 839/865 sapiensphosphoglycerate kinase 1 (PGK1), mRNA 282 235 U00238gi|404860|gb|U00238.1|U00238 Homo 1132 3600 0 653/677 sapiens glutaminePRPP amidotransferase (GPAT) mRNA, complete cds 283 237 NM_002753gi|4506080|ref|NM_002753.1|Homo 733 2372 0 381/385 sapiensmitogen-activated protein kinase 10 (MAPK10), mRNA 284 241 XM_006151gi|12736568|ref|XM_006151.2|Homo 979 1640 0 494/494 sapiens similar toserine protease, umbilical endothelium (H. sapiens) (LOC63320), mRNA 285242 BC004215 gi|13278917|gb|BC004215.1|BC004215 1106 3373 0 578/585 Homosapiens, eukaryotic translation elongation factor 1 gamma, clone MGC:4501, mRNA, complete cds 286 243 NM_000455gi|4507270|ref|NM_000455.1|Homo 1243 2158 0 651/660 sapiensserine/threonine kinase 11 (Peutz-Jeghers syndrome) (STK11), mRNA 287258 XM_004842 gi|12733228|ref|XM_004842.2|Homo 682 3715 0 381/387sapiens SFRS protein kinase 2 (SRPK2), mRNA 288 261 NM_020197gi|9910273|ref|NM_020197.1|Homo 561 1694 1E−158 346/355 sapiens HSKM-Bprotein (HSKM-B), mRNA 289 260 XM_001416gi|12719345|ref|XM_001416.2|Homo 517 2966 1E−145 277/284 sapiens similarto ribosomal protein S6 kinase, 90 kD, polypeptide 1 (H. sapiens)(LOC65290), mRNA 290 236 BC002499 gi|12803360|gb|BC002499.1|BC002499 6182129 1E−175 358/366 Homo sapiens, serine/threonine kinase 15, clone MGC:1605, mRNA, complete cds 293 246 XM_004679gi|11419466|ref|XM_004679.1|Homo 383 987 1E−104 214/224 sapienscyclin-dependent kinase 5 (CDK5), mRNA 294 245 XM_005258gi|11426310|ref|XM_005258.1|Homo 902 2391 0 463/466 sapiensserum/glucocorticoid regulated kinase-like (SGKL), mRNA 295 248XM_008654 gi|12740227|ref|XM_008654.2|Homo 662 3576 0 369/374 sapiensmitogen-activated protein kinase kinase 4 (MAP2K4), mRNA 296 129BC002364 gi|12803120|gb|BC002364.1|BC002364 688 2645 0 347/347 Homosapiens, non-POU-domain- containing, octamer-binding, clone MGC: 8677,mRNA, complete cds 298 2 NM_004443 gi|4758287|ref|NM_004443.1|Homo 5333805 1E−150 297/301 sapiens EphB3 (EPHB3) mRNA 299 254 XM_002383gi|11429253|ref|XM_002383.1|Homo 571 2832 1E−161 333/340 sapiens activinA receptor, type I (ACVR1), mRNA 300 249 BC000633gi|12653696|gb|BC000633.1|BC000633 537 2993 1E−151 396/419 Homo sapiens,TTK protein kinase, clone MGC: 865, mRNA, complete cds 301 2 NM_004443gi|4758287|ref|NM_004443.1|Homo 795 3805 0 453/467 sapiens EphB3 (EPHB3)mRNA 302 224 XM_005116 gi|12734122|ref|XM_005116.2|Homo 470 3396 1E−131252/259 sapiens protein tyrosine kinase 2 beta (PTK2B), mRNA 303 222AB056389 gi|13358639|dbj|AB056389.1|AB056389 196 2038 9E−49 129/141Macaca fascicularis brain cDNA, clone: QflA-12365 304 208 BC002921gi|12804134|gb|BC002921.1|BC002921 446 2349 1E−123 260/274 Homo sapiens,Similar to protein kinase related to S. cerevisiae STE20, effector forCdc42Hs, clone MGC: 10333, mRNA, complete cds 305 250 XM_004079gi|11417431|ref|XM_004079.1|Homo 525 1719 1E−147 275/280 sapiensserine/threonine-protein kinase PRP4 homolog (PRP4), mRNA 306 251XM_004306 gi|11418576|ref|XM_004306.1|Homo 317 7375 4E−85 160/160sapiens v-ros avian UR2 sarcoma virus oncogene homolog 1 (ROS1), mRNA307 252 BC004937 gi|13436283|gb|BC004937.1|BC004937 975 1032 0 567/582Homo sapiens, clone MGC: 10779, mRNA, complete cds 308 253 NM_006293gi|5454141|ref|NM_006293.1|Homo 823 4364 0 457/466 sapiens TYRO3 proteintyrosine kinase (TYRO3), mRNA 309 257 X71765gi|402221|emb|X71765.1|PFCAATPAS 38.2 5477 1.4 19/19 P. falciparum genefor Ca2+ - ATPase

Example 2 Detection of Differential Expression Using Arrays

mRNA isolated from samples of cancerous and normal colon tissue obtainedfrom patients were analyzed to identify genes differentially expressedin cancerous and normal cells. Normal and cancerous cells collected fromcryopreserved patient tissues were isolated using laser capturemicrodissection (LCM) techniques, which techniques are well known in theart (see, e.g., Ohyama et al. (2000) Biotechniques 29:530-6; Curran etal. (2000) Mol. Pathol. 53:64-8; Suarez-Quian et al. (1999)Biotechniques 26:328-35; Simone et al. (1998) Trends Genet. 14:272-6;Conia et al. (1997) J. Clin. Lab. Anal. 11:28-38; Emmert-Buck et al.(1996) Science 274:998-1001).

Tables 4A and 4B provide information about each patient from which thesamples were isolated, including: the “Patient ID” and “Path ReportID”,which are numbers assigned to the patient and the pathology reports foridentification purposes; the “Group” to which the patients have beenassigned; the anatomical location of the tumor (“Anatom Loc”); the“Primary Tumor Size”; the “Primary Tumor Grade”; the identification ofthe histopathological grade (“Histopath Grade”); a description of localsites to which the tumor had invaded (“Local Invasion”); the presence oflymph node metastases (“Lymph Node Met”); the incidence of lymph nodemetastases (provided as a number of lymph nodes positive for metastasisover the number of lymph nodes examined) (“Incidence Lymphnode Met”);the “Regional Lymphnode Grade”; the identification or detection ofmetastases to sites distant to the tumor and their location (“DistantMet & Loc”); a description of the distant metastases (“Descrip DistantMet”); the grade of distant metastasis (“Dist Met Grade”); and generalcomments about the patient or the tumor (“Comments”). Adenoma was notdescribed in any of the patients; adenoma dysplasia (described ashyperplasia by the pathologist) was described in Patient ID No. 695.Extranodal extensions were described in two patients, Patient ID Nos.784 and 791. Lymphovascular invasion was described in seven patients,Patient ID Nos. 128, 278, 517, 534, 784, 786, and 791. Crohn's-likeinfiltrates were described in seven patients, Patient ID Nos. 52, 264,268, 392, 393, 784, and 791.

TABLE 4A Path Primary Primary Patient Report Tumor Tumor Histopath ID IDGroup Anatom Loc Size Grade Grade Local Invasion 15 21 III Ascending 4T3 G2 extending into colon subserosal adipose tissue 52 71 II Ascending9 T3 G3 Invasion through colon muscularis propria, subserosalinvolvement; ileocec. valve involvement 121 140 II Sigmoid 6 T4 G2Invasion of muscularis propria into serosa, involving submucosa ofurinary bladder 125 144 II Cecum 6 T3 G2 Invasion through the muscularispropria into suserosal adipose tissue. Ileocecal junction. 128 147 IIITransverse 5 T3 G2 Invasion of colon muscularis propria into percolonicfat 130 149 Splenic 5.5 T3 through wall and into flexure surroundingadipose tissue 133 152 II Rectum 5 T3 G2 Invasion through muscularispropria into non- peritonealized pericolic tissue; gross configurationis annular. 141 160 IV Cecum 5.5 T3 G2 Invasion of muscularis propriainto pericolonic adipose tissue, but not through serosa. Arising fromtubular adenoma. 156 175 III Hepatic 3.8 T3 G2 Invasion through flexuremucsularis propria into subserosa/pericolic adipose, no serosalinvolvement. Gross configuration annular. 228 247 III Rectum 5.8 T3 G2to G3 Invasion through muscularis propria to involve subserosal,perirectoal adipose, and serosa 264 283 II Ascending 5.5 T3 G2 Invasionthrough colon muscularis propria into subserosal adipose tissue. 266 285III Transverse 9 T3 G2 Invades through colon muscularis propria toinvolve pericolonic adipose, extends to serosa. 268 287 I Cecum 6.5 T2G2 Invades full thickness of muscularis propria, but mesenteric adiposefree of malignancy 278 297 III Rectum 4 T3 G2 Invasion into perirectaladipose tissue. 295 314 II Ascending 5 T3 G2 Invasion through colonmuscularis propria into percolic adipose tissue. 339 358 II Rectosigmoid6 T3 G2 Extends into perirectal fat but does not reach serosa 341 360 IIAscending 2 cm T3 G2 Invasion through colon invasive muscularis propriato involve pericolonic fat. Arising from villous adenoma. 356 375 IISigmoid 6.5 T3 G2 Through colon wall into subserosal adipose tissue. Noserosal spread seen. 360 412 III Ascending 4.3 T3 G2 Invasion thru colonmuscularis propria to pericolonic fat 392 444 IV Ascending 2 T3 G2Invasion through colon muscularis propria into subserosal adiposetissue, not serosa. 393 445 II Cecum 6 T3 G2 Cecum, invades throughmuscularis propria to involve subserosal adipose tissue but not serosa.413 465 IV Ascending 4.8 T3 G2 Invasive through colon muscularis toinvolve periserosal fat; abutting ileocecal junction. 505 383 IV 7.5 cmT3 G2 Invasion through max dim muscularis propria involving pericolicadipose, serosal surface uninvolved 517 395 IV Sigmoid 3 T3 G2penetrates muscularis propria, involves pericolonic fat. 534 553 IIAscending 12 T3 G3 Invasion through the colon muscularis propriainvolving pericolic fat. Serosa free of tumor. 546 565 IV Ascending 5.5T3 G2 Invasion through colon muscularis propria extensively throughsubmucosal and extending to serosa. 577 596 II Cecum 11.5 T3 G2 Invasionthrough the bowel wall, into suberosal adipose. Serosal surface free oftumor. 695 714 II Cecum 14 T3 G2 extending through bowel wall intoserosal fat 784 803 IV Ascending 3.5 T3 G3 through muscularis colonpropria into pericolic soft tissues 786 805 IV Descending 9.5 T3 G2through muscularis colon propria into pericolic fat, but not at serosalsurface 791 810 IV Ascending 5.8 T3 G3 through the colon muscularispropria into pericolic fat 888 908 IV Ascending 2 T2 G1 into musculariscolon propria 889 909 IV Cecum 4.8 T3 G2 through muscularis propria intsubserosal tissue

TABLE 4B Incidence Regional Descrip Dist Patient Lymphnode LymphnodeLympnode Distant Met Distant Met ID Met Met Grade & Loc Met GradeComment 15 positive 8-Mar N1 negative MX invasive adenocarcinoma,moderately differentiated; focal perineural invasion is seen 52 negative0/12 N0 negative M0 Hyperplastic polyp in appendix. 121 negative 0/34 N0negative M0 Perineural invasion; donut anastomosis negative. Onetubulovillous and one tubular adenoma with no high grade dysplasia. 125negative 0/19 N0 negative M0 patient history of metastatic melanoma 128positive 5-Jan N1 negative M0 130 positive 24-Oct N2 negative M1 133negative 0/9  N0 negative M0 Small separate tubular adenoma (0.4 cm) 141positive 21-Jul N2 positive adenocarcinoma M1 Perineural invasion(Liver) consistant identified adjacent to with primary metastaticadenocarcinoma. 156 positive 13-Feb N1 negative M0 Separatetubolovillous and tubular adenomas 228 positive 8-Jan N1 negative MXHyperplastic polyps 264 negative 0/10 N0 negative M0 Tubulovillousadenoma with high grade dysplasia 266 negative 0/15 N1 positive 0.4 cm,may MX (Mesenteric represent deposit) lymph node completely replaced bytumor 268 negative 0/12 N0 negative M0 278 positive 10-Jul N2 negativeM0 Descending colon polyps, no HGD or carcinoma identified. 295 negative0/12 N0 negative M0 Melanosis coli and diverticular disease. 339negative 0/6  N0 negative M0 1 hyperplastic polyp identified 341negative 0/4  N0 negative MX 356 negative 0/4  N0 negative M0 360positive 5-Jan N1 negative M0 Two mucosal polyps 392 positive 6-Jan N1positive Macrovesicular M1 Tumor arising at (Liver) and prior ileocolicmicrovesicular surgical anastomosis. steatosis 393 negative 0/21 N0negative M0 413 negative 0/7  N0 positive adenocarcinoma M1 rediagnosisof (Liver) in multiple oophorectomy path to slides metastatic coloncancer. 505 positive 17-Feb N1 positive moderately M1 Anatomicallocation (Liver) differentiated of primary not adenocarcinoma, notatedin report. consistant Evidence of chronic with primary colitis. 517positive 6-Jun N2 negative M0 No mention of distant met in report 534negative 0/8  N0 negative M0 Omentum with fibrosis and fat necrosis.Small bowel with acute and chronic serositis, focal abscess andadhesions. 546 positive 12-Jun N2 positive metastatic M1 (Liver)adenocarcinoma 577 negative 0/58 N0 negative M0 Appendix dilated andfibrotic, but not involved by tumor 695 negative 0/22 N0 negative MXtubular adenoma and hyperplstic polyps present, moderatelydifferentiated adenoma with mucinous diferentiation (% not stated) 784positive 17-May N2 positive M1 invasive poorly (Liver) differentiatedadenosquamous carcinoma 786 negative 0/12 N0 positive M1 moderately(Liver) differentiated invasive adenocarcinoma 791 positive 13/25  N2positive M1 poorly differentiated (Liver) invasive colonicadenocarcinoma 888 positive 21-Mar N0 positive M1 well- to moderately-(Liver) differentiated adenocarcinoma; this patient has tumors of theascending colon and the sigmoid colon 889 positive 4-Jan N1 positive M1moderately (Liver) differentiated adenocarcinoma

Identification of Differentially Expressed Genes

cDNA probes were prepared from total RNA isolated from the patient cellsdescribed above. Since LCM provides for the isolation of specific celltypes to provide a substantially homogenous cell sample, this providedfor a similarly pure RNA sample.

Total RNA was first reverse transcribed into cDNA using a primercontaining a T7 RNA polymerase promoter, followed by second strand DNAsynthesis. cDNA was then transcribed in vitro to produce antisense RNAusing the T7 promoter-mediated expression (see, e.g., Luo et al. (1999)Nature Med 5:117-122), and the antisense RNA was then converted intocDNA. The second set of cDNAs were again transcribed in vitro, using theT7 promoter, to provide antisense RNA. Optionally, the RNA was againconverted into cDNA, allowing for up to a third round of T7-mediatedamplification to produce more antisense RNA. Thus the procedure providedfor two or three rounds of in vitro transcription to produce the finalRNA used for fluorescent labeling.

Fluorescent probes were generated by first adding control RNA to theantisense RNA mix, and producing fluorescently labeled cDNA from the RNAstarting material. Fluorescently labeled cDNAs prepared from the tumorRNA sample were compared to fluorescently labeled cDNAs prepared fromnormal cell RNA sample. For example, the cDNA probes from the normalcells were labeled with Cy3 fluorescent dye (green) and the cDNA probesprepared from the tumor cells were labeled with Cy5 fluorescent dye(red), and vice versa.

Each array used had an identical spatial layout and control spot set.Each microarray was divided into two areas, each area having an arraywith, on each half, twelve groupings of 32×12 spots, for a total ofabout 9,216 spots on each array. The two areas are spotted identicallywhich provide for at least two duplicates of each clone per array.

Polynucleotides for use on the arrays were obtained from both publiclyavailable sources and from cDNA libraries generated from selected celllines and patient tissues. PCR products of from about 0.5 kb to 2.0 kbamplified from these sources were spotted onto the array using aMolecular Dynamics Gen III spotter according to the manufacturer'srecommendations. The first row of each of the 24 regions on the arrayhad about 32 control spots, including 4 negative control spots and 8test polynucleotides. The test polynucleotides were spiked into eachsample before the labeling reaction with a range of concentrations from2-600 pg/slide and ratios of 1:1. For each array design, two slides werehybridized with the test samples reverse-labeled in the labelingreaction. This provided for about four duplicate measurements for eachclone, two of one color and two of the other, for each sample.

Table 5 describes the physical location of the differentially expressedpolynucleotides on the arrays. Table 5 includes: 1) a Spot ID, which isa unique identifier for each spot containing target sequence of intereston all arrays used; 2) a “Chip Num” which refers to a particular arrayrepresenting a specific set of genes; 3) the “Sample Name or Clone Name”from which the sequence was obtained; and 4) the coordinates of thesequence on the particular array (“Coordinates”). Table 6 providesinformation about the sequences on the arrays, specifically: 1)Candidate Identification Number; 2) Sample name or clone name; 3)function of the gene corresponding to the sequence (as determined byhomology to genes of known function by BLAST search of GenBank); 4) theclass of the gene (as determined by homology to genes of known functionby BLAST search of GenBank); 5) the pathway in which the gene isimplicated; 6) gene assignment; which refers to the gene to which thesequence has the greatest homology or identity; 7) the “Gene Symbol”; 8)chromosome number on which the gene is located (“Chrom Num”); 9) the mapposition on the chromosome.

TABLE 5 Chip SpotID Num Sample Name or Clone Name Coords 27 1M00023371A:G03 1:85  195 1 M00001489B:G04 1:227 212 1 M00026888A:A031:244 335 1 M00001558C:B06 1:367 511 1 M00003852B:C01 2:191 538 1M00022009A:A12 2:218 599 1 M00001374A:A06 2:279 943 1 M00001341B:A113:271 1048 1 M00007965C:G08 3:376 1160 1 M00022140A:E11 4:136 1176 1M00022180D:E11 4:152 1195 1 M00001675B:G05 4:171 1203 1 M00003853B:G114:179 1252 1 M00022742A:F08 4:228 1266 1 M00026900D:F02 4:242 1605 1M00001496A:G03 5:229 1648 1 M00001393D:F01 5:272 1793 1 M00023283C:C066:65  1927 1 M00007985A:B08 6:199 1933 1 M00007985B:A03 6:205 2332 1M00026903D:D11 7:252 2404 1 M00006883D:H12 7:324 2633 1 M00007987D:D048:201 2659 1 M00023431B:A01 8:227 2662 1 M00023363C:A04 8:230 2799 1M00004031B:D12 8:367 2889 1 M00003814C:C11 9:105 2917 1 M00007935D:A059:133 3005 1 M00021956B:A09 9:221 3204 1 M00027066B:E09 10:68  3296 1M00022215C:A10 10:160  3313 1 M00003961B:H05 10:177  3519 1M00005360A:A07 10:383  3665 1 M00001600C:B11 11:177  3748 1M00001402B:C12 11:260  3974 1 M00022168B:F02 12:134  4040 1M00008049B:A12 12:200  8594 2 RG:742775:10011:A07 1:178 8630 2I:2458926:03B01:C07 1:214 8788 2 I:3229778:02B01:B07 1:372 8840 2I:1857563:05B02:D01 2:72  9042 2 I:4072558:12B01:A07 2:274 9191 2I:1421929:05A01:D02 3:71  9349 2 I:1723834:01A01:C02 3:229 9478 2I:1817434:02B01:C02 3:358 9489 2 I:1750782:02A01:A08 3:369 9547 2I:1297179:05A02:F02 4:75  9684 2 I:1443877:03B02:B08 4:212 9724 2I:1384823:01B02:F08 4:252 9739 2 I:2902903:12A02:F02 4:267 9809 2I:2152363:04A02:A08 4:337 10000 2 RG:813679:10011:H03 5:176 10006 2RG:759927:10011:C09 5:182 10153 2 I:1712592:04A01:E03 5:329 10168 2I:2615513:04B01:D09 5:344 10200 2 I:1702266:02B01:D09 5:376 10299 2I:2825369:07A02:F09 6:123 10394 2 I:1450639:03B02:E09 6:218 10426 2I:2499976:01B02:E09 6:250 10600 2 I:1749883:05B01:D04 7:72  10614 2I:1516301:05B01:C10 7:86  10621 2 I:1298021:05A01:G10 7:93  10744 2I:1613615:03B01:D10 7:216 10877 2 I:1395918:04A01:G10 7:349 10956 2I:1600586:05B02:F04 8:76  10984 2 I:1666080:07B02:D04 8:104 11017 2I:1633286:06A02:E04 8:137 11019 2 I:1609538:06A02:F04 8:139 11035 2I:1630804:06A02:F10 8:155 11223 2 I:1749417:04A02:D10 8:343 11245 2I:1809385:02A02:G04 8:365 11258 2 I:1854245:02B02:E10 8:378 11445 2I:1854558:03A01:C11 9:213 11569 2 I:1509602:04A01:A11 9:337 11739 2I:1699587:06A02:F11 10:155  11838 2 I:2840195:01B02:G11 10:254  11908 2I:2914719:04B02:B05 10:324  11923 2 I:2239819:04A02:B11 10:339  12001 2I:2483109:05A01:A06 11:65  12007 2 I:2499479:05A01:D06 11:71  12013 2I:2675481:05A01:G06 11:77  12104 2 RG:773612:10011:D06 11:168  12270 2I:2914605:04B01:G06 11:334  12513 2 I:2079906:01A02:A06 12:225  12519 2I:1810640:01A02:D06 12:231  16933 3 I:1963753:18B01:E07 1:122 17035 3RG:166410:10006:F01 1:171 17059 3 I:1920650:16A01:B01 1:195 17068 3I:1923769:16B01:F01 1:204 17069 3 I:901317:16A01:G01 1:205 17075 3I:3518380:16A01:B07 1:211 17171 3 RG:666323:10010:B07 1:307 17385 3RG:244132:10007:E01 2:169 17386 3 RG:2117694:10016:E01 2:170 17399 3RG:241029:10007:D07 2:183 17459 3 I:2056395:13A02:B07 2:243 17533 3RG:1555877:10013:G07 2:317 17696 3 I:1923490:18B01:H08 3:128 17730 3RG:526536:10002:A02 3:162 17742 3 RG:612874:10002:G02 3:174 17746 3RG:530002:10002:A08 3:178 17836 3 RG:29739:10004:F02 3:268 17964 3I:1920522:15B02:F02 4:44  18089 3 RG:244601:10007:E02 4:169 18100 3RG:2048081:10016:B08 4:180 18102 3 RG:2097294:10016:C08 4:182 18240 3RG:1927470:10015:H08 4:320 18331 3 I:1926006:15A01:F09 5:59  18379 3I:2359588:18A01:F03 5:107 18389 3 I:986558:18A01:C09 5:117 18408 3I:970933:14B01:D03 5:136 18445 3 RG:180296:10006:G03 5:173 18488 3I:1743234:16B01:D09 5:216 18552 3 RG:25258:10004:D09 5:280 18580 3RG:985973:10012:B09 5:308 18801 3 RG:203031:10007:A09 6:177 18804 3RG:2055807:10016:B09 6:180 18856 3 I:605019:13B02:D03 6:232 18886 3RG:43296:10005:C03 6:262 18903 3 RG:301608:10008:D09 6:279 18904 3RG:45623:10005:D09 6:280 18921 3 RG:1461567:10013:E03 6:297 18942 3RG:1895716:10015:G09 6:318 18985 3 I:1402615:09A02:E03 6:361 19067 3I:2054678:19A01:F10 7:91  19120 3 I:956077:14B01:H04 7:144 19175 3I:750899:16A01:D04 7:199 19189 3 I:620494:16A01:C10 7:213 19229 3I:2060725:13A01:G10 7:253 19264 3 RG:35892:10004:H10 7:288 19374 3I:1758241:15B02:G04 8:46  19428 3 I:1965257:18B02:B04 8:100 19590 3RG:43534:10005:C04 8:262 19600 3 RG:110764:10005:H04 8:272 19603 3RG:278409:10008:B10 8:275 19604 3 RG:41097:10005:B10 8:276 19629 3RG:1552386:10013:G04 8:301 19642 3 RG:1838677:10015:E10 8:314 19766 3I:1996180:19B01:C11 9:86  19816 3 I:1431819:14B01:D05 9:136 19821 3I:1833191:14A01:G05 9:141 19822 3 I:1227385:14B01:G05 9:142 19835 3I:2055926:14A01:F11 9:155 19950 3 RG:32281:10004:G05 9:270 19962 3RG:27403:10004:E11 9:282 19971 3 RG:665682:10010:B05 9:291 20102 3I:2759046:19B02:C05 10:70  20196 3 RG:2012168:10016:B05 10:164  20280 3I:1960722:13B02:D11 10:248  20303 3 RG:343821:10008:H05 10:271  20315 3RG:323425:10008:F11 10:283  20506 3 I:1969044:18B01:E12 11:122  20586 3I:659143:16B01:E06 11:202  20691 3 RG:669110:10010:B12 11:307  20703 3RG:740831:10010:H12 11:319  20775 3 I:1968921:15A02:D06 12:39  20878 3I:998612:14B02:G06 12:142  20915 3 RG:208954:10007:B12 12:179  20940 3I:1967543:16B02:F06 12:204  21017 3 RG:306813:10008:E12 12:281  21025 3RG:1353123:10013:A06 12:289  21068 3 I:549299:17B02:F06 12:332  21160 4RG:1996901:20003:D01 1:104 21207 4 M00056483D:G07 1:151 21294 4M00042439D:C11 1:238 21354 4 RG:781507:10011:E01 1:298 21518 4RG:1374447:20004:G01 2:110 21544 4 M00056908A:H05 2:136 21589 4M00054777D:E09 2:181 21674 4 RG:2002384:20003:E01 2:266 21705 4RG:1651303:10014:E01 2:297 21732 4 M00054538C:C01 2:324 21763 4M00056622B:F12 2:355 21769 4 M00056632B:H10 2:361 21784 4 M00055423A:C072:376 21812 4 M00056308A:F02 3:52  21884 4 RG:2006302:20003:F08 3:12421921 4 M00054639D:F05 3:161 21983 4 M00057081B:H03 3:223 22023 4M00056533D:G07 3:263 22027 4 M00056534C:E08 3:267 22043 4 M00056585B:F043:283 22060 4 RG:785846:10011:F02 3:300 22072 4 RG:781028:10011:D083:312 22254 4 M00056918C:F09 4:142 22285 4 M00054742C:B12 4:173 22299 4M00054806B:G03 4:187 22366 4 M00056350B:B03 4:254 22375 4 M00056728C:G024:263 22405 4 RG:1637619:10014:C02 4:293 22415 4 RG:1674393:10014:H024:303 22419 4 RG:1635546:10014:B08 4:307 22498 4 M00056250C:B02 5:34 22619 4 M00056500C:A07 5:155 22633 4 M00054647A:A09 5:169 22678 4M00057231A:G04 5:214 22724 4 RG:1861510:20001:B03 5:260 22775 4RG:417109:10009:D09 5:311 22783 4 RG:487171:10009:H09 5:319 23103 4M00056810A:A02 6:287 23179 4 M00056645C:D11 6:363 23183 4 M00056646B:F076:367 23189 4 M00056679B:H03 6:373 23286 4 RG:1996788:20003:C10 7:11823337 4 M00054650D:E04 7:169 23371 4 M00057044D:G03 7:203 23373 4M00057046A:G09 7:205 23380 4 M00057241C:F03 7:212 23394 4 M00042756A:H027:226 23471 4 RG:471154:10009:H04 7:303 23514 4 M00054520A:D04 7:34623803 4 M00056812D:A08 8:283 23813 4 RG:1638979:10014:C04 8:293 23984 4RG:2051667:20003:H05 9:112 24185 4 RG:432960:10009:E11 9:313 24186 4RG:785368:10011:E11 9:314 24297 4 M00055209C:B07 10:73  24358 4M00056937C:C10 10:134  24394 4 M00056992C:F12 10:170  24423 4M00057126C:B03 10:199  24429 4 M00057127B:B09 10:205  24515 4RG:1630930:10014:B05 10:291  24519 4 RG:1645945:10014:D05 10:295  247004 RG:2006592:20003:F12 11:124  24713 4 M00056478D:B07 11:137  24728 4M00056227B:G06 11:152  24806 4 M00042770D:G04 11:230  24855 4M00056619A:H02 11:279  24866 4 RG:742764:10011:A06 11:290  24867 4RG:364972:10009:B06 11:291  24883 4 RG:376554:10009:B12 11:307  24900 4M00054500D:C08 11:324  24944 4 M00054971D:D07 11:368  25021 4M00055258B:D12 12:93  25095 4 M00054769A:E05 12:167  25161 4M00055435B:A12 12:233  25203 4 M00056822A:E08 12:275  25212 4RG:2006592:20003:F12 12:284  25219 4 RG:1631867:10014:B06 12:291  253054 M00056707D:D05 12:377  25309 4 M00056709B:D03 12:381  25332 4M00055583C:B07 1:55  25337 4 M00056301D:A04 1:60  25393 2I:2606813:04A02:B12 12:339  25430 2 I:1931371:02B02:D12 12:376 

TABLE 6 Chro- mo- Sample Name or Gene some Map CID Clone Name FunctionClass Pathway GeneAssignment Symbol Num Position 1 I:1222317:15A02:C02Unknown Ca++ Homo sapiens S100 S100A 1 1q12-q22 binding calcium-bindingprotein A4 (calcium protein, calvasculin, metastasin, murine placentalhomolog) (S100A4) mRNA > :: gb|M80563|HUMCAPL Human CAPL protein mRNA,complete cds. 2 I:1227385:14B01:G05 Signal kinase EphB3 [Homo sapiens]EPHB3 3 3q21 Transduction 2 RG:32281:10004:G05 Signal kinase EphB3 [Homosapiens] EPHB3 3 3q21 Transduction 2 RG:41097:10005:B10 Signal kinaseEphB3 [Homo sapiens] EPHB3 3 3q21 Transduction 3 I:1297179:05A02:F02Metabolism dehydrogenase folate methylene- MTHFD1 14 14q24 pathwaytetrahydrofolate dehydrogenase (NADP+ dependent),methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolatesynthetase 4 I:1298021:05A01:G10 Cell Cycle pseudouridine rRNAdyskeratosis congenital, DKC1 X Xq28 (psi) processing dyskerin synthase5 I:1358285:04A02:F11 Signal kinase AXL receptor tyrosine AXL 19 19q13.1Transduction kinase 5 M00022180D:E11 Signal kinase AXL receptor tyrosineAXL 19 19q13.1 Transduction kinase 6 I:1384823:01B02:F08 Cell CycleCDC28 CDC28 protein kinase 2 CKS2 9 9q22 subunit 7 I:1395918:04A01:G10Cytoskeleton GTPase Arg/Abl-interacting ARGBP2 4 4 protein ArgBP2 8I:1402615:09A02:E03 Cell Cycle ubiquitination Fn14 for type I LOC5133016 16 transmenmbrane protein 9 I:1421929:05A01:D02 Adhesion cadherincadherin 3, P-cadherin CDH3 16 16q22 (placental) 10 I:1431819:14B01:D05GTPase nucleolar P130 10 phosphoprotein p130 11 I:1443877:03B02:B08Protein proteasome 26S proteasome- POH1 2 2 Degradation subunitassociated pad1 homolog 12 I:1450639:03B02:E09 microtubule- caltractin(20 kD CALT X Xq28 organizing calcium-binding protein) 13I:1480159:06B02:E03 Unknown protease kallikrein 6 (neurosin, KLK6 1919q13.3 zyme) 14 I:1509602:04A01:A11 Metabolism lipoxygenase arachdonicarachidonate 5- ALOX5 10 10q11.2 metabolism lipoxygenase 15I:1516301:05B01:C10 Transcription transcription forkhead box M1 FOXM1 1212p13 factor 16 I:1600586:05B02:F04 RNA spliceosome splicing factor 3b,SF3B3 splicing subunit 3, 130 kD 17 I:1609538:06A02:F04 Mitochondrialtranslocase translocase of outer TOM34 20 20 mitochondrial 20 membrane34 18 I:1613615:03B01:D10 Signal secreted bone morphogenetic BMP4 1414q22-q23 Transduction protein 4 19 I:1630804:06A02:F10 Metabolism ironFriedreich ataxia FRDA 9 9q13-q21.1 homeostasis 20 I:1633286:06A02:E04Unknown membrane transmembrane 4 TM4SF4 3 3 superfamily member 4 21I:1666080:07B02:D04 Unknown novel 22 I:1699587:06A02:F11 Unknownprotease matrix MMP7 11 11q21-q22 metalloproteinase 7 (matrilysin,uterine) 23 I:1702266:02B01:D09 Metabolism carboxylate amino acidpyrroline-5-carboxylate PYCR1 17 17 reductase synthesis reductase 1 24I:1712592:04A01:E03 insulin induced gene 1 INSIG1 7 7q36 25I:1723834:01A01:C02 cell cycle transcription minichromosome MCM2 3 3q21factor maintenance deficient (S. cerevisiae) 2 (mitotin) 26I:1743234:16B01:D09 Novel secreted 27 I:1749417:04A02:D10 Unknownprotease cathepsin H CTSH 15 15q24-q25 28 I:1749883:05B01:D04 Metabolismkinase pyridoxal (pyridoxine, PDXK 21 21q22.3 vitamin B6) kinase 29I:1750782:02A01:A08 Unknown novel KIAA0007 protein KIAA0007 2 2 30I:1758241:15B02:G04 Cell Cycle CDC28 CDC28 protein kinase 1 CKS1 8 8q21kinase 30 M00056227B:G06 Cell Cycle CDC28 CDC28 protein kinase 1 CKS1 88q21 kinase 31 I:1809385:02A02:G04 integrin- integrin beta 3 bindingITGB3BP 1 1 binding protein (beta3- pathway endonexin) [Homo sapiens] 32I:1810640:01A02:D06 Adhesion kinase EphA1 EPHA1 7 7q32-q36 33I:1817434:02B01:C02 Nucleotide transketolase transketolase TKT 3 3p14.3Biosynthesis (Wernicke-Korsakoff syndrome) 34 I:1833191:14A01:G05Unknown dedicator of cytokinesis 3 DOCK3 3 3 35 I:1854245:02B02:E10Unknown kinase KIAA0173 gene KIAA0173 2 2 product [Homo sapiens] 36I:1854558:03A01:C11 Metabolism glycosylation fucosyltransferase 1 FUT119 19q13.3 (galactoside 2-alpha-L- fucosyltransferase, Bombay phenotypeincluded) 37 I:1857563:05B02:D01 transcription 6-pyruvoyl- PCBD 10 10q22factor tetrahydropterin synthase/dimerization cofactor of hepatocytenuclear factor 1 alpha (TCF1) 38 I:1920522:15B02:F02 Cell Cycle D123gene product D123 39 I:1920650:16A01:B01 Ca++ annexin A3 ANXA3 44q13-q22 signal 41 I:1923490:18B01:H08 Unknown phosphatase hypotheticalprotein LOC51235 1 1 41 M00022742A:F08 Unknown phosphatase hypotheticalprotein LOC51235 1 1 42 I:1923769:16B01:F01 Unknown unknown hypotheticalprotein, HSA272196 17 17q11.2 clone 2746033 43 I:1926006:15A01:F09 DNAmismatch mutS (E. coli) homolog 6 MSH6 2 2p16 Repair repair 44I:1931371:02B02:D12 Unknown microtubule- KIAA0097 gene KIAA0097 11 11organizing product 45 I:1960722:13B02:D11 Chaperone HSP90 tumor necrosisfactor LOC51721 16 16 type 1 receptor associated protein [Homo sapiens]46 I:1963753:18B01:E07 Trafficking membrane transporter 47I:1965257:18B02:B04 Unknown novel 48 I:1967543:16B02:F06 Novel secreted13 13 49 I:1968921:15A02:D06 Adhesion cell surface immunoglobulin ISLR15 15q23-q24 superfamily containing leucine-rich repea 50I:1969044:18B01:E12 Unknown kinase 51 I:1981218:16B02:H01 Unknowntransmembrane integral type I protein P24B 15 15q24-q25 53I:1996180:19B01:C11 Signal GTP Transduction effector 54I:2054678:19A01:F10 Unknown Ca++ 1 1 binding 55 I:2055926:14A01:F11Unknown kinase thymidine kinase 1, TK1 17 17q23.2-q25.3 soluble 56I:2056395:13A02:B07 Adhesion fasciclin transforming growth TGFBI 5 5q31factor, beta-induced, 68 kD 58 I:2060725:13A01:G10 Ca++ calcyclinbinding CACYBP 1 1q24-q25 signal protein [Homo sapiens] 59I:2079906:01A02:A06 DNA replication Replication factor 60I:2152363:04A02:A08 Unknown kinase non-metastatic cells 1, NME1 1717q21.3 protein (NM23A) expressed in 63 I:2239819:04A02:B11 Unknownprotease dipeptidase 1 (renal) DPEP1 16 16q24.3 64 I:2359588:18A01:F03Unknown unknown 65 I:2458926:03B01:C07 Unknown novel KIAA0101 geneKIAA0101 15 15 product [Homo sapiens] 65 M00055423A:C07 Unknown novelKIAA0101 gene KIAA0101 15 15 product [Homo sapiens] 66I:2483109:05A01:A06 Unknown kinase chromosome 1 open C1ORF2 1 1q21reading frame 2 67 I:2499479:05A01:D06 Transcription transcriptionfactor NRF NRF 68 I:2499976:01B02:E09 transmembrane 70I:2606813:04A02:B12 Chaperone isomerase peptidylprolyl PPIE 1 1p32isomerase E (cyclophilin E) 71 I:2615513:04B01:D09 antizyme polyamineantizyme inhibitor LOC51582 inhibitor synthesis [Homo sapiens] 74I:2675481:05A01:G06 Mitochondrial protease ClpP (caseinolytic CLPP 19 19protease, ATP- dependent, proteolytic subunit, E. coli) homolog 75I:2759046:19B02:C05 Unknown membrane tetraspan 5 TSPAN-5 4 4 76I:2825369:07A02:F09 Metabolism transferase serine phosphoserine PSA 9 9biosynthesis aminotransferase 77 I:2840195:01B02:G11 Nucleotide kinaseadenosine kinase ADK 10 10cen-q24 Biosynthesis 78 I:2902903:12A02:F02Adhesion transmembrane interferon induced IFITM1 11 11 transmembraneprotein 1 (9-27) 79 I:2914605:04B01:G06 Unknown unknown KIAA0170 geneKIAA0170 6 6p21.3 product [Homo sapiens] 80 I:2914719:04B02:B05 nuclearRAE1 (RNA export 1, RAE1 20 20 export S. pombe) homolog 81I:3229778:02B01:B07 Adhesion integrin integrin, alpha 2 ITGA2 5 5q23-31(CD49B, alpha 2 subunit of VLA-2 receptor) 83 I:3518380:16A01:B07Metabolism sterol cholesterol 7-dehydrocholesterol DHCR7 1111q13.2-q13.5 reductase biosynthesis reductase 85 I:4072558:12B01:A07Translation initiation factor 87 I:549299:17B02:F06 Novel KIAA0784protein KIAA0784 20 20q13.13-q13.2 88 I:605019:13B02:D03 Unknowntransferase catechol-O- COMT 22 22q11.21 methyltransferase 89I:620494:16A01:C10 Unknown proteasome proteasome (prosome, PSMB7 99q34.11-q34.12 subunit macropain) subunit, beta type, 7 90I:659143:16B01:E06 Unknown novel 91 I:750899:16A01:D04 Unknownphosphatase protein tyrosine PTPRN 2 2q35-q36.1 phosphatase, receptortype, N 92 I:763607:16A01:E09 Unknown unknown tumor protein D52-like 1TPD52L1 6 6q22-q23 93 I:901317:16A01:G01 Unknown proteasome proteasome(prosome, PSMB4 1 1q21 subunit macropain) subunit, beta type, 4 94I:956077:14B01:H04 DNA GTPase nudix (nucleoside NUDT1 7 7p22 Repairdiphosphate linked moiety X)-type motif 1 95 I:970933:14B01:D03 Novelsecreted FOXJ2 forkhead factor LOC55810 96 I:986558:18A01:C09 Unknownunknown 3 98 I:998612:14B02:G06 Metabolism dehydrogenase3-phosphoglycerate PHGDH 1 1p11.1-13.1 dehydrogenase 100 M00001341B:A11Cell Cycle kinase KIAA0175 gene KIAA0175 9 9 product [Homo sapiens] 101M00001349A:C11 Adhesion kinase discoidin domain DDR1 6 6p21.3 receptorfamily, member 1 102 M00001351C:E02 Unknown unknown cathepsin C CTSC 1111q14.1-q14.3 103 M00001374A:A06 Unknown desaturase stearoyl-CoA SCD 1010 desaturase 104 M00001393D:F01 Metabolism dehydrogenase lactatedehydrogenase B LDHB 12 12p12.2-p12.1 105 M00001402B:C12 Cell Cyclekinase cyclin-dependent CDK4 12 12q14 kinase 4 106 M00001402C:B01Unknown unknown catenin (cadherin- CTNNAL1 9 9q31.2 associated protein),alpha-like 1 109 M00001489B:G04 HSPC003 protein HSPC003 [Homo sapiens]110 M00001496A:G03 Transcription transcription v-myb avian MYBL2 2020q13.1 factor myeloblastosis viral oncogene homolog-like 2 111M00001558C:B06 Unknown novel hypothetical protein HSPC130 20 20 112M00001600C:B11 helicase DEAD-box protein ABS 5 5 abstrakt [Homo sapiens]113 M00001675B:G05 Novel GTPase KIAA0712 gene KIAA0712 11 11 product[Homo sapiens] 114 M00003814C:C11 Unknown novel KIAA0116 proteinKIAA0116 3 3 115 M00003852B:C01 Signal cytokine prostate differentiationPLAB 19 19p13.1-13.2 Transduction factor 116 M00003853B:G11 Unknownnovel 20 20 117 M00003961B:H05 Unknown kinase EphB4 EPHB4 7 7 118M00004031B:D12 Unknown secreted 118 M00057112B:E11 Unknown secreted 120M00004229C:B06 Unknown protease cathepsin Z CTSZ 20 20q13 121M00005360A:A07 Novel calcitonin EGF-like-domain, EGFL2 1 1 receptormultiple 2 122 M00005438D:D06 Unknown protease beta-site APP-cleavingBACE2 21 21q22.3 enzyme 2 123 M00006883D:H12 Unknown novel 124M00007935D:A05 Unknown novel 7 7 125 M00007965C:G08 Unknown unknown 126M00007985A:B08 Unknown novel 1 1 127 M00007985B:A03 sigma sigma receptorSR-BP1 9 9 receptor (SR31747 binding protein 1) 128 M00007987D:D04 Novelsecreted KIAA0179 KIAA0179 21 21q22.3 129 M00008049B:A12 RNA non-Poudomain- NONO X Xq13.1 Splicing containing octamer (ATGCAAAT) bindingprotein [Homo sapiens] 129 RG:25258:10004:D09 RNA non-Pou domain- NONO XXq13.1 Splicing containing octamer (ATGCAAAT) binding protein [Homosapiens] 130 M00008099D:A05 Unknown secreted 20 20 131 M00021828C:F04Unknown kinase dual-specificity DYRK4 12 12 tyrosine-(Y)-phosphorylation regulated kinase 4 132 M00021956B:A09 Transcriptiontranscription ets variant gene 4 (E1A ETV4 17 17q21 factorenhancer-binding protein, E1AF) 133 M00022009A:A12 Unknown unknownpleckstrin homology- PHLDA1 12 12q15 like domain, family A, member 1 134M00022081D:G02 Unknown kinase Ste20-related KIAA0204 10 10serine/threonine kinase [Homo sapiens] 135 M00022158D:C11 Adhesionlaminin laminin, beta 3 (nicein LAMB3 1 1q32 (125 kD), kalinin (140 kD),BM600 (125 kD)) 136 M00022168B:F02 Unknown deaminase hypotheticalprotein FLJ10540 FLJ10540 137 M00022215C:A10 Unknown unknown 138M00023283C:C06 Unknown novel hypothetical protein HN1L 16 16 similar tomouse HN1 (Hematological and Neurological expressed sequence 1) 139M00023363C:A04 Unknown protease kallikrein 11 KLK11 19 19q13.3-q13.4 140M00023371A:G03 Cell Cycle retinoblastoma-binding RBBP8 18 18q11.2protein 8 141 M00023431B:A01 Ribosomal small 6 6q14.3-16.2 Biogenesisnucleolar RNA 142 M00026888A:A03 Unknown novel 143 M00026900D:F02Metabolism transferase sulfotransferase family SULT2B1 19 19q13.3 2B,member 1 144 M00026903D:D11 Metabolism kinase galactokinase 1 GALK1 1717q24 145 M00027066B:E09 Unknown unknown 146 M00032537B:F11 Unknowntransmembrane 147 M00042439D:C11 Cell Cycle ubiquitin ubiquitin carrierprotein UBCH10 20 20 carrier E2-C 148 M00042704D:D09 Unknown novel 149M00042756A:H02 Cell Cycle SET translocation SET 9 9q34 (myeloidleukemia- associated) 150 M00042770D:G04 hypothetical protein MAC30 1717 151 M00042818A:D05 Unknown integrase 151 M00054520A:D04 Unknownintegrase 152 M00054500D:C08 Unknown proteasome proteasome (prosome,PSMA7 subunit macropain) subunit, alpha type, 7 153 M00054538C:C01Autophagy Apg12 (autophagy 12, APG12L 5 5q21-q22 S. cerevisiae)-like 154M00054639D:F05 GTP nucleocyto karyopherin (importin) KPNB3 bindingplasmic beta 3 transport? 155 M00054647A:A09 Metabolism glyoxalaseglyoxalase I GLO1 6 6p21.3-p21.1 156 M00054650D:E04 Ribosomal RNA, U22small RNU22 11 11q13 Biogenesis nucleolar 157 M00054742C:B12 Unknowncytokine macrophage migration MIF 22 22q11.23 inhibitory factor(glycosylation- inhibiting factor) 158 M00054769A:E05 Translationribosomal ribosomal protein S3A RPS3A 4 4q31.2-q31.3 protein 159M00054777D:E09 Unknown secreted carcinoembryonic CEACAM6 19 19q13.2antigen-related cell adhesion molecule 6 (non-specific cross reactingantigen) 160 M00054806B:G03 Unknown snRNA 161 M00054893C:D03 Unknownnovel putative nucleotide E2IG3 binding protein, estradiol-induced [Homosapiens] 162 M00054971D:D07 Unknown novel 20 20q13.2-13.2 163M00055135A:B06 Unknown unknown hypothetical protein HSPC011 [Homosapiens] 164 M00055258B:D12 interferon induced IFITM2 11 11transmembrane protein 2 (1-8D) 165 M00055406C:D03 Unknown kinaseCDC-like kinase 1 CLK1 2 2q33 166 M00055435B:A12 Apoptosis unknownover-expressed breast OBTP tumor protein 167 M00055583C:B07 Novelsecreted hypothetical protein LOC51316 [Homo sapiens] 169 M00055873C:B06Unknown protease secretory leukocyte SLPI inhibitor protease inhibitor(antileukoproteinase) 170 M00056250C:B02 transmembrane pituitary tumor-PTTG1 5 5q35.1 transforming 1 171 M00056301D:A04 Unknown unknown 172M00056308A:F02 sulfate/ down-regulated in DRA 7 7q31 oxalate adenomaTransporter? 173 M00056350B:B03 Cytoskeleton Ca++ S100 calcium-bindingS100A11 1 1q21 binding protein A11 (calgizzarin) 174 M00056423A:B06Unknown novel hypothetical protein HSPC148 11 11 [Homo sapiens] 175M00056478D:B07 Unknown novel clone HQ0310 LOC51203 15 15 PRO0310p1 [Homosapiens] 176 M00056483D:G07 Unknown protease kallikrein 10 KLK10 1919q13 176 M00057046A:G09 Unknown protease kallikrein 10 KLK10 19 19q13177 M00056500C:A07 nascent-polypeptide- NACA 12 12q23-q24.1 associatedcomplex alpha polypeptide 178 M00056533D:G07 Unknown secretedDKFZP434G032 DKFZP434G032 17 17 protein [Homo sapiens] 179M00056534C:E08 Signal secreted amphiregulin AREG 4 4q13-q21 Transduction(schwannoma-derived growth factor) 180 M00056585B:F04 Unknown hydrolasegamma-glutamyl GGH hydrolase (conjugase, folylpolygammaglutamylhydrolase) 181 M00056617D:F07 Unknown novel 182 M00056619A:H02Cytoskeleton plastin plastin 3 (T isoform) PLS3 X X 183 M00056622B:F12DNA topoisomerase topoisomerase (DNA) TOP2A 17 17q21-q22 Replication IIalpha (170 kD) 184 M00056632B:H10 ATP/GTP chromosome 20 open C20ORF1 2020q11.2 binding reading frame 1 185 M00056645C:D11 Metabolism peroxidaseoxidative glutathione peroxidase 1 GPX1 3 3p21.3 metabolism 186M00056646B:F07 ribosomal protein L7a RPL7A 9 9q33-q34 187 M00056679B:H03nucleophosmin NPM1 5 5q35 (nucleolar phosphoprotein B23, numatrin) 188M00056707D:D05 Unknown novel 189 M00056709B:D03 Unknown novel CGI-138protein LOC51649 17 17 [Homo sapiens] 190 M00056728C:G02 Cell Cycle MAD2(mitotic arrest MAD2L1 4 4q27 deficient, yeast, homolog)-like 1 191M00056732B:E02 Unknown novel LIM domain only 7 LMO7 13 13 192M00056810A:A02 Novel GTP hypothetical protein PTD004 binding 193M00056812D:A08 Unknown hydrolase S- AHCY 20 20cen-q13.1adenosylhomocysteine hydrolase 194 M00056822A:E08 Signal RAS-like RAN,member RAS RAN 6 6p21 Transduction oncogene family 195 M00055209C:B07Unknown novel 7 7p14-p15 195 M00056908A:H05 Unknown novel 7 7p14-p15 196M00056918C:F09 Unknown novel hypothetical protein HSPC152 11 11 [Homosapiens] 197 M00056937C:C10 Cell Cycle Ca++ S100 calcium-binding S100P 44p16 binding protein P 198 M00056953B:C09 Unknown proteasome proteasome(prosome, PSME2 14 14q11.2 subunit macropain) activator subunit 2 (PA28beta) 199 M00056992C:F12 Unknown unknown 200 M00057044D:G03 Unknownunknown 6 6 201 M00057081B:H03 Unknown unknown ribosomal protein L10aRPL10A 202 M00057086D:D08 Unknown unknown RNA binding motif RBM8 1 1q12protein 8 203 M00057126C:B03 Unknown novel 204 M00057127B:B09 Unknownunknown 205 M00057192B:D02 Unknown unknown 206 M00057231A:G04Transcription transcription non-metastatic cells 2, NME2 17 17q21.3factor protein (NM23B) expressed in 206 RG:1651303:10014:E01Transcription transcription non-metastatic cells 2, NME2 17 17q21.3factor protein (NM23B) expressed in 207 M00057241C:F03 Translationinitiation eukaryotic translation EIF3S6 8 8q22-q23 factor initiationfactor 3, subunit 6 (48 kD) 208 RG:110764:10005:H04 kinase proteinkinase related PAK4 19 19 to S. cerevisiae STE20, effector for Cdc42Hs210 RG:1325847:10012:H07 Unknown transmembrane 6 6q23 212RG:1353123:10013:A06 Cell Cycle phosphatase cyclin-dependent CDKN3 1414q22 kinase inhibitor 3 (CDK2-associated dual specificity phosphatase)212 RG:1637619:10014:C02 Cell Cycle phosphatase cyclin-dependent CDKN314 14q22 kinase inhibitor 3 (CDK2-associated dual specificityphosphatase) 213 RG:1374447:20004:G01 Unknown novel 214RG:1461567:10013:E03 Cell Cycle kinase budding uninhibited by BUB1 22q14 benzimidazoles 1 (yeast homolog) 215 RG:1525813:10013:F12 Unknownnovel 2 2 216 RG:1552386:10013:G04 phosphatase acid phosphatase 1, ACP12 2p25 soluble 217 RG:1555877:10013:G07 Metabolism NADPH neutrophilcytosolic NCF4 22 22q13.1 oxidase factor 4 (40 kD), isoform 1 [Homosapiens] 218 RG:1630930:10014:B05 nucleic kinase deoxythymidylate DTYMK2 2 acid kinase synthesis 219 RG:1631867:10014:B06 DNA Ku protein dsDNAX-ray repair XRCC5 2 2q35 Repair repair complementing defective repairin Chinese hamster cells 5 (double-strand-break rejoining; Kuautoantigen, 80 kD) 220 RG:1638979:10014:C04 Metabolism GST drugglutathione S- GSTP1 11 11q13 metabolism transferase pi 221RG:1645945:10014:D05 proteasome proteasome (prosome, PSMA2 6 6q27subunit macropain) subunit, alpha type, 2 221 RG:1674393:10014:H02proteasome proteasome (prosome, PSMA2 6 6q27 subunit macropain) subunit,alpha type, 2 222 RG:166410:10006:F01 Novel kinase 223RG:1674098:10014:H01 Unknown unknown myristoylated alanine- MACS 66q22.2 rich protein kinase C substrate (MARCKS, 80K-L) 224RG:180296:10006:G03 kinase protein tyrosine kinase PTK2B 8 8p21.1 2 beta225 RG:1838677:10015:E10 kinase membrane-associated PKMYT1 tyrosine- andthreonine-specific cdc2-inhibitory kinase 226 RG:1861510:20001:B03Unknown novel 227 RG:1895716:10015:G09 Novel kinase 14 14 228RG:1927470:10015:H08 Metabolism kinase glycolysis phosphoglycerate PGK1X Xq13 kinase 1 229 RG:1996788:20003:C10 Unknown novel 230RG:1996901:20003:D01 Unknown novel 231 RG:2002384:20003:E01 Unknownnovel 232 RG:2006302:20003:F08 Unknown novel 233 RG:2006592:20003:F12Unknown novel 12 235 RG:2012168:10016:B05 Metabolism hydrolasephosphoribosyl PPAT 4 4q12 pyrophosphate amidotransferase 236RG:203031:10007:A09 Unknown kinase serine/threonine kinase STK15 2020q13.2-q13.3 15 236 RG:781507:10011:E01 Unknown kinase serine/threoninekinase STK15 20 20q13.2-q13.3 15 237 RG:2048081:10016:B08 kinasemitogen-activated MAPK10 protein kinase 10 238 RG:2051667:20003:H05Unknown novel 1 1 239 RG:2055807:10016:B09 Unknown kinase 20 20p12.2-13240 RG:208954:10007:B12 kinase Xq25-26.3 241 RG:2097257:10016:C07Unknown protease serine protease, SPUVE 12 12 umbilical endothelium 242RG:2097294:10016:C08 Mitochondrial transferase thymidylate serine SHMT212 12q12-q14 synthase hydroxymethyl- metabolic transferase cycle 2(mitochondrial) 243 RG:2117694:10016:E01 Unknown kinase serine/threoninekinase STK11 19 19p13.3 11 (Peutz-Jeghers syndrome) 244RG:241029:10007:D07 Unknown kinase serine/threonine kinase STK12 1717p13.1 12 245 RG:244132:10007:E01 kinase serum/glucocorticoid SGKL 88q12.3-8q13.1 regulated kinase-like 246 RG:244601:10007:E02 Cell Cyclekinase cyclin-dependent CDK5 7 7q36 kinase 5 247 RG:27403:10004:E11Novel transmembrane 248 RG:278409:10008:B10 Unknown kinasemitogen-activated MAP2K4 17 17p11.2 protein kinase kinase 4 249RG:29739:10004:F02 Cell Cycle kinase TTK protein kinase TTK 6 6q13-q21250 RG:301608:10008:D09 kinase serine/threonine- PRP4 protein kinasePRP4 homolog 251 RG:306813:10008:E12 kinase v-ros avian UR2 ROS1 6 6q22sarcoma virus oncogene homolog 1 252 RG:1635546:10014:B08 Ribosomalnucleolar protein NOP56 20 20 Biogenesis (KKE/D repeat) 252RG:323425:10008:F11 Ribosomal nucleolar protein NOP56 20 20 Biogenesis(KKE/D repeat) 253 RG:343821:10008:H05 kinase TYRO3 protein TYRO3 1515q15.1-q21.1 tyrosine kinase 254 RG:35892:10004:H10 kinase activin Areceptor, type I ACVR1 2 2q23-q24 255 RG:364972:10009:B06 Unknown novel19 19 256 RG:376554:10009:B12 Unknown novel 8 8 257 RG:417109:10009:D09Unknown novel 9 9 258 RG:43296:10005:C03 kinase SFRS protein kinase 2SRPK2 7 7q22-q31.1 259 RG:432960:10009:E11 Transcription deacetylaseretinoblastoma-binding RBBP7 protein 7 260 RG:43534:10005:C04 kinaseribosomal protein S6 RPS6KA1 3 3 kinase, 90 kD, polypeptide 1 261RG:45623:10005:D09 Unknown novel HSKM-B protein HSKM-B 262RG:471154:10009:H04 protease tissue inhibitor of TIMP3 22 22q12.3inhibitor metalloproteinase 3 (Sorsby fundus dystrophy,pseudoinflammatory) 263 RG:487171:10009:H09 Unknown kinase polo(Drosophia)-like PLK kinase 264 RG:526536:10002:A02 kinase solutecarrier family 9 SLC9A3R2 16 16p13.3 (sodium/hydrogen exchanger),isoform 3 regulatory factor 2 265 RG:530002:10002:A08 kinase EphA3 EPHA33 3p11.2 266 RG:612874:10002:G02 kinase serum-inducible kinase SNK 5 5267 RG:665547:10010:B04 Unknown novel 2 2 268 RG:665682:10010:B05Unknown kinase mitogen-activated MAP2K7 protein kinase kinase 7 269RG:666323:10010:B07 kinase sterile-alpha motif and ZAK 2 2q24.2 leucinezipper containing kinase AZK [Homo sapiens] 270 RG:669110:10010:B12Novel kinase 271 RG:686594:10010:D03 Cell Cycle kinase KIAA0965 proteinKIAA0965 12 12 273 RG:729913:10010:G11 Unknown kinase 14 14 274RG:740831:10010:H12 kinase v-raf murine sarcoma ARAF1 X Xp11.4-p11.23611 viral oncogene homolog 1 276 RG:742764:10011:A06 RNA splicingfactor, SFRS3 splicing arginine/serine-rich 3 277 RG:781028:10011:D08kinase mitogen-activated MAP4K3 protein kinase kinase kinase kinase 3278 RG:785368:10011:E11 Novel kinase PDZ-binding kinase; T- TOPK 88p21-p12 cell originated protein kinase 278 RG:785846:10011:F02 Novelkinase PDZ-binding kinase; T- TOPK 8 8p21-p12 cell originated proteinkinase 280 RG:985973:10012:B09 Unknown kinase v-akt murine thymoma AKT31 1q43-q44 viral oncogene homolog 3 (protein kinase B, gamma) 291M00022140A:E11 Chaperone HSP90 heat shock 90 kD HSPCB 6 6p12 protein 1,beta M00054510D:F09 RG:742775:10011:A07 RG:759927:10011:C09RG:773612:10011:D06 RG:813679:10011:H03

The differential expression assay was performed by mixing equal amountsof probes from tumor cells and normal cells of the same patient. Thearrays were prehybridized by incubation for about 2 hrs at 60° C. in5×SSC/0.2% SDS/1 mM EDTA, and then washed three times in water and twicein isopropanol. Following prehybridization of the array, the probemixture was then hybridized to the array under conditions of highstringency (overnight at 42° C. in 50% formamide, 5×SSC, and 0.2% SDS.After hybridization, the array was washed at 55° C. three times asfollows: 1) first wash in lx SSC/0.2% SDS; 2) second wash in0.1×SSC/0.2% SDS; and 3) third wash in 0.1×SSC.

The arrays were then scanned for green and red fluorescence using aMolecular Dynamics Generation III dual color laser-scanner/detector. Theimages were processed using BioDiscovery Autogene software, and the datafrom each scan set normalized to provide for a ratio of expressionrelative to normal. Data from the microarray experiments was analyzedaccording to the algorithms described in U.S. application Ser. No.60/252,358, filed Nov. 20, 2000, by E. J. Moler, M. A. Boyle, and F. M.Randazzo, and entitled “Precision and accuracy in cDNA microarray data,”which application is specifically incorporated herein by reference.

The experiment was repeated, this time labeling the two probes with theopposite color in order to perform the assay in both “color directions.”Each experiment was sometimes repeated with two more slides (one in eachcolor direction). The level fluorescence for each sequence on the arrayexpressed as a ratio of the geometric mean of 8 replicate spots/genesfrom the four arrays or 4 replicate spots/gene from 2 arrays or someother permutation. The data were normalized using the spiked positivecontrols present in each duplicated area, and the precision of thisnormalization was included in the final determination of thesignificance of each differential. The fluorescent intensity of eachspot was also compared to the negative controls in each duplicated areato determine which spots have detected significant expression levels ineach sample.

A statistical analysis of the fluorescent intensities was applied toeach set of duplicate spots to assess the precision and significance ofeach differential measurement, resulting in a p-value testing the nullhypothesis that there is no differential in the expression level betweenthe tumor and normal samples of each patient. During initial analysis ofthe microarrays, the hypothesis was accepted if p>10⁻³, and thedifferential ratio was set to 1.000 for those spots. All other spotshave a significant difference in expression between the tumor and normalsample. If the tumor sample has detectable expression and the normaldoes not, the ratio is truncated at 1000 since the value for expressionin the normal sample would be zero, and the ratio would not be amathematically useful value (e.g., infinity). If the normal sample hasdetectable expression and the tumor does not, the ratio is truncated to0.001, since the value for expression in the tumor sample would be zeroand the ratio would not be a mathematically useful value. These lattertwo situations are referred to herein as “on/off.” Database tables werepopulated using a 95% confidence level (p>0.05).

Table 7 (incorporated by reference to a compact disk) provides theresults for gene products differentially expressed in the colon tumorsamples relative to normal tissue samples. Table 7 includes: 1) the SEQID NO; 2) the CID or candidate identification number; 3) the spotidentification number (“SpotID”); 4) the percentage of patients testedin which expression levels of the gene was at least 2-fold greater incancerous tissue than in matched normal tissue (“>=2×”); 5) thepercentage of patients tested in which expression levels of the gene wasat least 2.5-fold greater in cancerous tissue than in matched normaltissue (“>=2.5×”); 6) the percentage of patients tested in whichexpression levels of the gene was at least 5-fold greater in canceroustissue than in matched normal cells (“>=5×”); 7) the percentage ofpatients tested in which expression levels of the gene was less than orequal to ½ of the expression level in matched normal cells (“<=half×”);and 8) the number of patients tested for each sequence. Table 7 alsoincludes the results from each patient, identified by the patient IDnumber (e.g., “15Ratio”). This data represents the ratio of differentialexpression for the samples tested from that particular patient's tissues(e.g., “15Ratio” is the ratio from the tissue samples of patient ID no.15). The ratios of differential expression is expressed as a normalizedhybridization signal associated with the tumor probe divided by thenormalized hybridization signal with the normal probe. Thus, a ratiogreater than 1 indicates that the gene product is increased inexpression in cancerous cells relative to normal cells, while a ratio ofless than 1 indicates the opposite.

These data provide evidence that the genes represented by thepolynucleotides having the indicated sequences are differentiallyexpressed in colon cancer.

Example 3 Antisense Regulation of Gene Expression

The expression of the differentially expressed genes represented by thepolynucleotides in the cancerous cells was analyzed using antisenseknockout technology to confirm the role and function of the gene productin tumorigenesis, e.g., in promoting a metastatic phenotype.

A number of different oligonucleotides complementary to the mRNAgenerated by the differentially expressed genes identified herein weredesigned as potential antisense oligonucleotides, and tested for theirability to suppress expression of the genes. Sets of antisense oligomersspecific to each candidate target were designed using the sequences ofthe polynucleotides corresponding to a differentially expressed gene andthe software program HYB simulator Version 4 (available for Windows95/Windows NT or for Power Macintosh, RNAture, Inc. 1003 Health SciencesRoad, West, Irvine, Calif. 92612 USA). Factors considered when designingantisense oligonucleotides include: 1) the secondary structure ofoligonucleotides; 2) the secondary structure of the target gene; 3) thespecificity with no or minimum cross-hybridization to other expressedgenes; 4) stability; 5) length and 6) terminal GC content. The antisenseoligonucleotide is designed to so that it will hybridize to its targetsequence under conditions of high stringency at physiologicaltemperatures (e.g., an optimal temperature for the cells in culture toprovide for hybridization in the cell, e.g., about 37° C.), but withminimal formation of homodimers.

Using the sets of oligomers and the HYB simulator program, three to tenantisense oligonucleotides and their reverse controls were designed andsynthesized for each candidate mRNA transcript, which transcript wasobtained from the gene corresponding to the target polynucleotidesequence of interest. Once synthesized and quantitated, the oligomerswere screened for efficiency of a transcript knock-out in a panel ofcancer cell lines. The efficiency of the knock-out was determined byanalyzing mRNA levels using lightcycler quantification. The oligomersthat resulted in the highest level of transcript knock-out, wherein thelevel was at least about 50%, preferably about 80-90%, up to 95% or moreup to undetectable message, were selected for use in a cell-basedproliferation assay, an anchorage independent growth assay, and anapoptosis assay.

The ability of each designed antisense oligonucleotide to inhibit geneexpression was tested through transfection into SW620 colon colorectalcarcinoma cells. For each transfection mixture, a carrier molecule,preferably a lipitoid or cholesteroid, was prepared to a workingconcentration of 0.5 mM in water, sonicated to yield a uniform solution,and filtered through a 0.45 μm PVDF membrane. The antisense or controloligonucleotide was then prepared to a working concentration of 100 μMin sterile Millipore water. The oligonucleotide was further diluted inOptiMEM™ (Gibco/BRL), in a microfuge tube, to 2 μM, or approximately 20μg oligo/ml of OptiMEM™. In a separate microfuge tube, lipitoid orcholesteroid, typically in the amount of about 1.5-2 nmol lipitoid/μgantisense oligonucleotide, was diluted into the same volume of OptiMEM™used to dilute the oligonucleotide. The diluted antisenseoligonucleotide was immediately added to the diluted lipitoid and mixedby pipetting up and down. Oligonucleotide was added to the cells to afinal concentration of 30 nM.

The level of target mRNA that corresponds to a target gene of interestin the transfected cells was quantitated in the cancer cell lines usingthe Roche LightCycler™ real-time PCR machine. Values for the target mRNAwere normalized versus an internal control (e.g., beta-actin). For each20 μl reaction, extracted RNA (generally 0.2-1 μg total) was placed intoa sterile 0.5 or 1.5 ml microcentrifuge tube, and water was added to atotal volume of 12.5 To each tube was added 7.5 μl of a buffer/enzymemixture, prepared by mixing (in the order listed) 2.5 μl H₂O, 2.0 μl 10×reaction buffer, 10 μl oligo dT (20 μmol), 1.0 μl dNTP mix (10 mM each),0.5 μl RNAsin® (20 u) (Ambion, Inc., Hialeah, Fla.), and 0.5 μl MMLVreverse transcriptase (50 u) (Ambion, Inc.). The contents were mixed bypipetting up and down, and the reaction mixture was incubated at 42° C.for 1 hour. The contents of each tube were centrifuged prior toamplification.

An amplification mixture was prepared by mixing in the following order:1×PCR buffer II, 3 mM MgCl₂, 140 μM each dNTP, 0.175 μmol each oligo,1:50,000 dil of SYBR® Green, 0.25 mg/ml BSA, 1 unit Taq polymerase, andH₂O to 20 (PCR buffer II is available in 10× concentration fromPerkin-Elmer, Norwalk, Conn.). In 1× concentration it contains 10 mMTris pH 8.3 and 50 mM KCl. SYBR® Green (Molecular Probes, Eugene, Oreg.)is a dye which fluoresces when bound to double stranded DNA. As doublestranded PCR product is produced during amplification, the fluorescencefrom SYBR® Green increases. To each 20 μl aliquot of amplificationmixture, 2 μl of template RT was added, and amplification was carriedout according to standard protocols.

The results of the antisense assays are provided in Table 8. The resultsare expressed as the percent decrease in expression of the correspondinggene product relative to non-transfected cells, vehicle-only transfected(mock-transfected) cells, or cells transfected with reverse controloligonucleotides. Table 8 includes: 1) the SEQ ID NO; 2) the CID; 3) the“Gene Assignment” which refers to the gene to which the sequence has thegreatest homology or identity; 4) the “Gene Symbol”; 5) GenBank genename; and 6) the percent decrease in expression of the gene relative tocontrol cells (“mRNA KO”).

TABLE 8 SEQ ID Gene GenBank mRNA NO CID GeneAssignment Symbol Gene NameKO  4 1 Homo sapiens S100 calcium-binding protein S100A S100A4 >80% A4(calcium protein, calvasculin, metastasin, murine placental homolog)(S100A4) mRNA > :: gb|M80563|HUMCAPL Human CAPL protein mRNA, completecds.  9 6 CDC28 protein kinase 2 CKS2 CKS2 01/ >80% 11  11 8 Fn14 fortype I transmenmbrane protein LOC51330 Fn14 >90%  12 9 cadherin 3,P-cadherin (placental) CDH3 CADHERIN-P >90%  16 13 kallikrein 6(neurosin, zyme) KLK6 proteaseM >80%  17 14 arachidonate 5-lipoxygenaseALOX5 ALOX5 >80%  22 18 bone morphogenetic protein 4 BMP4 BMP4 >90%  2521 GSTHOM >90%  32 27 cathepsin H CTSH CATH-H >90%  38 33 transketolase(Wernicke-Korsakoff TKT TRANSKETOLASE >90% syndrome)  41 36fucosyltransferase 1 (galactoside 2-alpha-L- FUT1 FUT1 >90%fucosyltransferase, Bombay phenotype included)  42 376-pyruvoyl-tetrahydropterin PCBD hDohc >95% synthase/dimerizationcofactor of hepatocyte nuclear factor 1 alpha (TCF1)  54 50THC271862 >70%  56 53 hECT2 >80%  63 63 dipeptidase 1 (renal) DPEP1DPP >80%  71 74 ClpP (caseinolytic protease, ATP-dependent, CLPPCLPP >80% proteolytic subunit, E. coli) homolog  77 75 tetraspan 5TSPAN-5 NET-4 >90%  78 76 phosphoserine aminotransferase PSA serAT >90% 87 121 EGF-like-domain, multiple 2 EGFL2 EGFL2 >70% 100 127 sigmareceptor (SR31747 binding protein 1) SR-BP1 SR-BP1 >90% 113 92 tumorprotein D52-like 1 TPD52L1 hD53 >80% 141 143 sulfotransferase family 2B,member 1 SULT2B1 SULT2B1 >80% 147 166 over-expressed breast tumorprotein OBTP HUMTUM >90% 165 179 amphiregulin (schwannoma-derived growthAREG AREG >90% factor) 180 193 S-adenosylhomocysteine hydrolase AHCYHUMAHCY2 >70% 183 196 hypothetical protein [Homo sapiens] HSPC152c719 >80% 208 155 glyoxalase I GLO1 GLO1 >90% 213 160 c374641 >80% 214161 putative nucleotide binding protein, E2IG3 c454001 >80%estradiol-induced [Homo sapiens] 218 164 interferon inducedtransmembrane protein 2 IFITM2 1-8U >90% (1-8D) 233 263 polo(Drosophia)-like kinase PLK PLK1 >90% 236 266 serum-inducible kinase SNKSNK >80% 239 269 sterile-alpha motif and leucine zipper ZAK AZK >70%containing kinase AZK [Homo sapiens] 242 273 AA399596 >70% 253 280 v-aktmurine thymoma viral oncogene AKT3 AKT3 >90% homolog 3 (protein kinaseB, gamma) 276 227 ITAK1 >90% 279 239 AI335279 >90% 285 242 serinehydroxymethyltransferase 2 SHMT2 SHMT2 >90% (mitochondrial) 294 245serum/glucocorticoid regulated kinase-like SGKL SGKL >90% 295 248mitogen-activated protein kinase kinase 4 MAP2K4 MKK4 >80% 300 249 TTKprotein kinase TTK hTTK >90% 123, 124 103 stearoyl-CoA desaturase SCDSCD >90% 130, 228 115 prostate differentiation factor PLAB PLAB >80%162, 193 176 kallikrein 10 KLK10 NES1 >80% 182, 217 195 c1665 >80% 247,290 236 serine/threonine kinase 15 STK15 hARK2 >80% 257, 268 212cyclin-dependent kinase inhibitor 3 (CDK2- CDKN3 KAP >85% associateddual specificity phosphatase)  31, 151 170 pituitary tumor-transforming1 PTTG1 PTTG1 >90%  35, 150 30 CDC28 protein kinase 1 CKS1 CKS1 >80%  5,298, 301 2 EphB3 [Homo sapiens] EPHB3 EPHB3 >90%  65, 220 65 KIAA0101gene product [Homo sapiens] KIAA0101 KIAA0101 >80%  73, 116 100 KIAA0175gene product [Homo sapiens] KIAA0175 KIAA0175 >90%  75, 131, 134 106catenin (cadherin-associated protein), alpha- CTNNAL1RTA00000179AF.k.22.1 >90% like 1  8, 106 5 AXL receptor tyrosine kinaseAXL >95%  88, 196 118 c3376 >80%

Example 4 Effect of Expression on Proliferation

The effect of gene expression on the inhibition of cell proliferationwas assessed in metastatic breast cancer cell lines (MDA-MB-231(“231”)), SW620 colon colorectal carcinoma cells, or SKOV3 cells (ahuman ovarian carcinoma cell line).

Cells were plated to approximately 60-80% confluency in 96-well dishes.Antisense or reverse control oligonucleotide was diluted to 2 μM inOptiMEM™ and added to OptiMEM™ into which the delivery vehicle, lipitoid116-6 in the case of SW620 cells or 1:1 lipitoid 1:cholesteroid 1 in thecase of MDA-MB-231 cells, had been diluted. The oligo/delivery vehiclemixture was then further diluted into medium with serum on the cells.The final concentration of oligonucleotide for all experiments was 300nM, and the final ratio of oligo to delivery vehicle for all experimentswas 1.5 nmol lipitoid/μg oligonucleotide.

Antisense oligonucleotides were prepared as described above (see Example3). Cells were transfected overnight at 37° C. and the transfectionmixture was replaced with fresh medium the next morning. Transfectionwas carried out as described above in Example 3.

The results of the antisense experiments are shown in Table 9 (columnlabeled “Proliferation”). Those antisense oligonucleotides that resultedin decreased proliferation in SW620 colorectal carcinoma cells areindicated by “Inhib in” and “weak effect in”, with the cell typefollowing. Those antisense oligonucleotides that resulted in inhibitionof proliferation of SW620 cells indicates that the corresponding geneplays a role in production or maintenance of the cancerous phenotype incancerous colon cells. Those antisense oligonucleotides that inhibitedproliferation in SKOV3 cells represent genes that play a role inproduction or maintenance of the cancerous phenotype in cancerous breastcells. Those antisense oligonucleotides that resulted in inhibition ofproliferation of MDA-MB-231 cells indicates that the corresponding geneplays a role in production or maintenance of the cancerous phenotype incancerous ovarian cells.

TABLE 9 SEQ ID Gene mRNA NO CID GeneAssignment Symbol Gene KOProliferation Softagar  4 1 Homo sapiens S100 S100A S100A4 >80% Inhib inweak calcium-binding protein SW620 inhibition A4 (calcium protein,calvasculin, metastasin, murine placental homolog) (S100A4) mRNA > ::gb|M80563|HUMCAPL Human CAPL protein mRNA, complete cds.  11 8 Fn14 fortype I LOC51330 Fn14 >90% inconsis. inhibits transmenmbrane proteinSW620, SW620, 231 231  12 9 cadherin 3, P-cadherin CDH3 CADHERIN-P >90%Inhib in Inhib in (placental) SW620 SW620  16 13 kallikrein 6 (neurosin,KLK6 proteaseM >80% weak effect negative zyme) in SW620 SW620  38 33transketolase (Wernicke- TKT TRANSKETOLASE >90% inconsis. inhibitsKorsakoff syndrome) SW620, SW620, 231 231  42 37 6-pyruvoyl- PCBDhDohc >95% inconsis. inhibits tetrahydropterin SW620, SW620,synthase/dimerization 231 231 cofactor of hepatocyte nuclear factor 1alpha (TCF1)  56 53 hECT2 >80% Inhib in Inhib in SW620 SW620  63 63dipeptidase 1 (renal) DPEP1 DPP >80% weak negative inhibition in SW620 77 75 tetraspan 5 TSPAN-5 NET-4 >90% Inhib in weak SW620 inhibition 180193 S-adenosylhomocysteine AHCY HUMAHCY 2 >70% Inhib in Inhib inhydrolase SW620 SW620 233 263 polo (Drosophia)-like PLK PLK1 >90% Inhibin Inhib in kinase SW620 SW620 236 266 serum-inducible kinase SNKSNK >80% Inhib in negative SW620 in SW620 253 280 v-akt murine thymomaAKT3 AKT3 >90% inhibits inhibits viral oncogene homolog 3 SKOV3, 231SKOV3, (protein kinase B, gamma) 231 279 239 AI335279 >90% negative inweak SW620 inhibition 300 249 TTK protein kinase TTK hTTK >90% inhibitsinhibits SW620 SW620 247, 290 236 serine/threonine kinase 15 STK15hARK2 >80% Inhib in weak SW620 effect in SW620 257, 268 212cyclin-dependent kinase CDKN3 KAP >85% Inhib in inhibitor 3 (CDK2- SW620associated dual specificity phosphatase)  35, 150 30 CDC28 proteinkinase 1 CKS1 CKS1 >80% Inhib in Inhib in SW620 SW620  88, 196 118c3376 >80% weak effect neg in SW620 SW620

Example 5 Effect of Gene Expression on Colony Formation

The effect of gene expression upon colony formation of SW620 cells,SKOV3 cells, and MD-MBA-231 cells was tested in a soft agar assay. Softagar assays were conducted by first establishing a bottom layer of 2 mlof 0.6% agar in media plated fresh within a few hours of layering on thecells. The cell layer was formed on the bottom layer by removing cellstransfected as described above from plates using 0.05% trypsin andwashing twice in media. The cells were counted in a Coulter counter, andresuspended to 10⁶ per ml in media. 10 μl aliquots were placed withmedia in 96-well plates (to check counting with WST1), or dilutedfurther for the soft agar assay. 2000 cells were plated in 800 μl 0.4%agar in duplicate wells above 0.6% agar bottom layer. After the celllayer agar solidified, 2 ml of media was dribbled on top and antisenseor reverse control oligo (produced as described in Example 3) was addedwithout delivery vehicles. Fresh media and oligos were added every 3-4days. Colonies formed in 10 days to 3 weeks. Fields of colonies werecounted by eye. Wst-1 metabolism values can be used to compensate forsmall differences in starting cell number. Larger fields can be scannedfor visual record of differences.

Table 9 provides the results of these assays (“Softagar”). Thoseantisense oligonucleotides that resulted in inhibition of colonyformation are indicated by “inhibits”, “weak effect”, or “weakinhibition” followed by the cell type. Those antisense oligonucleotidesthat resulted in inhibition of colony formation of SW620 cells indicatesthat the corresponding gene plays a role in production or maintenance ofthe cancerous phenotype in cancerous colon cells. Those antisenseoligonucleotides that inhibited colony formation in SKOV3 cellsrepresent genes that play a role in production or maintenance of thecancerous phenotype in cancerous breast cells. Those antisenseoligonucleotides that resulted in inhibition of colony formation ofMDA-MB-231 cells indicates that the corresponding gene plays a role inproduction or maintenance of the cancerous phenotype in cancerousovarian cells.

Example 6 Induction of Cell Death Upon Depletion of Polypeptides byDepletion OF mRNA (“Antisense Knockout”)

In order to assess the effect of depletion of a target message upon celldeath, SW620 cells, or other cells derived from a cancer of interest,are transfected for proliferation assays. For cytotoxic effect in thepresence of cisplatin (cis), the same protocol is followed but cells areleft in the presence of 2 μM drug. Each day, cytotoxicity was monitoredby measuring the amount of LDH enzyme released in the medium due tomembrane damage. The activity of LDH is measured using the CytotoxicityDetection Kit from Roche Molecular Biochemicals. The data is provided asa ratio of LDH released in the medium vs. the total LDH present in thewell at the same time point and treatment (rLDH/tLDH). A positivecontrol using antisense and reverse control oligonucleotides for BCL2 (aknown anti-apoptotic gene) is included; loss of message for BCL2 leadsto an increase in cell death compared with treatment with the controloligonucleotide (background cytotoxicity due to transfection).

Example 7 Functional Analysis of Gene Products Differentially Expressedin Colon Cancer in Patients

The gene products of sequences of a gene differentially expressed incancerous cells can be further analyzed to confirm the role and functionof the gene product in tumorigenesis, e.g., in promoting or inhibitingdevelopment of a metastatic phenotype. For example, the function of geneproducts corresponding to genes identified herein can be assessed byblocking function of the gene products in the cell. For example, wherethe gene product is secreted or associated with a cell surface membrane,blocking antibodies can be generated and added to cells to examine theeffect upon the cell phenotype in the context of, for example, thetransformation of the cell to a cancerous, particularly a metastatic,phenotype.

Where the gene product of the differentially expressed genes identifiedherein exhibits sequence homology to a protein of known function (e.g.,to a specific kinase or protease) and/or to a protein family of knownfunction (e.g., contains a domain or other consensus sequence present ina protease family or in a kinase family), then the role of the geneproduct in tumorigenesis, as well as the activity of the gene product,can be examined using small molecules that inhibit or enhance functionof the corresponding protein or protein family.

Additional functional assays include, but are not necessarily limitedto, those that analyze the effect of expression of the correspondinggene upon cell cycle and cell migration. Methods for performing suchassays are well known in the art.

Example 8 Contig Assembly and Additional Gene Characterization

The sequences of the polynucleotides provided in the present inventioncan be used to extend the sequence information of the gene to which thepolynucleotides correspond (e.g., a gene, or mRNA encoded by the gene,having a sequence of the polynucleotide described herein). This expandedsequence information can in turn be used to further characterize thecorresponding gene, which in turn provides additional information aboutthe nature of the gene product (e.g., the normal function of the geneproduct). The additional information can serve to provide additionalevidence of the gene product's use as a therapeutic target, and providefurther guidance as to the types of agents that can modulate itsactivity.

In one example, a contig was assembled using the sequence of thepolynucleotide having SEQ ID NO:2 (sequence name 019.G3.sp6_(—)128473),which is present in clone M00006883D:H12. A “contig” is a contiguoussequence of nucleotides that is assembled from nucleic acid sequenceshaving overlapping (e.g., shared or substantially similar) sequenceinformation. The sequences of publicly-available ESTs (ExpressedSequence Tags) and the sequences of various clones from several cDNAlibraries synthesized at Chiron were used in the contig assembly. Noneof the sequences from these latter clones from the cDNA libraries hadsignificant hits against known genes with function when searched usingBLASTN against GenBank as described above.

The contig was assembled using the software program Sequencher, version4.05, according to the manufacturer's instructions. The final contig wasassembled from 11 sequences, provided in the Sequence Listing as SEQ IDNOS:2 and 310-320. The sequence names and SEQ ID NOS of the sequencesare provided in the overview alignment produced by Sequencher (see FIG.1).

The clone containing the sequence of 035JN032.H09 (SEQ ID NO:319) is ofparticular interest. This clone was originally obtained from anormalized cDNA library prepared from a prostate cancer tissue samplethat was obtained from a patient with Gleason grade 3+3. The clonehaving the 035JN032.H09 sequence corresponds to a gene that hasincreased expression in (e.g., is upregulated) in colon cancer asdetected by microarray analysis using the protocol and materialsdescribed above. The data is provided in Table 10 below.

TABLE 10 Number of patients used to SEQ calculate ID Spot Sample con- %% NO ID Chip # ID cordance >=2x >=5x 2 1833 1 M00006883D:H12 33 61 33319 27454 5 035JN032.H09 28 61 11

“%>2×” and “%>5×” indicate the percentage of patients in which thecorresponding gene was expressed at two-fold and five-fold greaterlevels in cancerous cells relative to normal cells, respectively.

This observation thus further validates the expression profile of theclone having the sequence of 035JN032.H09, as it indicates that the generepresented by this sequence and clone is differentially expressed in atleast two different cancer types.

The sequence information obtained in the contig assembly described abovewas used to obtain a consensus sequence derived from the contig usingthe Sequencher program. The consensus sequence is provided as SEQ IDNO:320 in the Sequence Listing.

In preliminary experiments, the consensus sequence was used as a querysequence in a BLASTN search of the DGTI DoubleTwist Gene Index(DoubleTwist, Inc., Oakland, Calif.), which contains all the EST andnon-redundant sequence in public databases. This preliminary searchindicated that the consensus sequence has homology to a predicted genehomologue to human atrophin-1 (HSS0190516.1 dtgic|HSC010416.3 Similarto: DRPL_HUMAN gi117660|sp|P54259|DRPL_HUMAN ATROPHIN-1(DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY PROTEIN) [Homo sapiens (Human),provided as SEQ ID NO:322), with a Score=1538 bits (776), Expect=0.0,and Identities=779/780 (99%).

While the preliminary results regarding the homology to atrophin-1 arenot yet confirmed, this example, through contig assembly and the use ofhomology searching software programs, shows that the sequenceinformation provided herein can be readily extended to confirm, orconfirm a predicted, gene having the sequence of the polynucleotidesdescribed in the present invention. Further the information obtained canbe used to identify the function of the gene product of the genecorresponding to the polynucleotides described herein. While notnecessary to the practice of the invention, identification of thefunction of the corresponding gene, can provide guidance in the designof therapeutics that target the gene to modulate its activity andmodulate the cancerous phenotype (e.g., inhibit metastasis,proliferation, and the like).

Example 9 Source of Biological Materials

The biological materials used in the experiments that led to the presentinvention are described below.

Source of Patient Tissue Samples

Normal and cancerous tissues were collected from patients using lasercapture microdis section (LCM) techniques, which techniques are wellknown in the art (see, e.g., Ohyama et al. (2000) Biotechniques29:530-6; Curran et al. (2000) Mol. Pathol. 53:64-8; Suarez-Quian et al.(1999) Biotechniques 26:328-35; Simone et al. (1998) Trends Genet.14:272-6; Conia et al. (1997) J. Clin. Lab. Anal. 11:28-38; Emmert-Bucket al. (1996) Science 274:9981001). Table 11 provides information abouteach patient from which colon tissue samples were isolated, including:the Patient ID (“PT ID”) and Path ReportlD (“Path ID”), which arenumbers assigned to the patient and the pathology reports foridentification purposes; the group (“Grp”) to which the patients havebeen assigned; the anatomical location of the tumor (“Anatom Loc”); theprimary tumor size (“Size”); the primary tumor grade (“Grade”); theidentification of the histopathological grade (“Histo Grade”); adescription of local sites to which the tumor had invaded (“LocalInvasion”); the presence of lymph node metastases (“Lymph Met”); theincidence of lymph node metastases (provided as a number of lymph nodespositive for metastasis over the number of lymph nodes examined) (“LymphMet Incid”); the regional lymphnode grade (“Reg Lymph Grade”); theidentification or detection of metastases to sites distant to the tumorand their location (“Dist Met & Loc”); the grade of distant metastasis(“Dist Met Grade”); and general comments about the patient or the tumor(“Comments”). Histophatology of all primary tumors indicated the tumorwas adenocarcinoma except for Patient ID Nos. 130 (for which noinformation was provided), 392 (in which greater than 50% of the cellswere mucinous carcinoma), and 784 (adenosquamous carcinoma). Extranodalextensions were described in three patients, Patient ID Nos. 784 and791. Lymphovascular invasion was described in Patient ID Nos. 128, 228,278, 517, 784, 786, 791, and 890. Crohn's-like infiltrates weredescribed in seven patients, Patient ID Nos. 52, 264, 268, 392, 393,784, and 791.

TABLE 11 Pt Path Histo ID ID Grp Anatom Loc Size Grade Grade LocalInvasion  15 21 III Ascending 4.0 T3 G2 Extending into colon subserosaladipose tissue  52 71 II Cecum 9.0 T3 G3 Invasion through muscularispropria, subserosal involvement; ileocec. valve involvement 121 140 IISigmoid 6 T4 G2 Invasion of muscularis propria into serosa, involvingsubmucosa of urinary bladder 125 144 II Cecum 6 T3 G2 Invasion throughthe muscularis propria into suserosal adipose tissue. Ileocecaljunction. 128 147 III Transverse 5.0 T3 G2 Invasion of colon muscularispropria into percolonic fat 130 149 Splenic 5.5 T3 through wall andflexure into surrounding adipose tissue 133 152 II Rectum 5.0 T3 G2Invasion through muscularis propria into non- peritonealized pericolictissue; gross configuration is annular. 141 160 IV Cecum 5.5 T3 G2Invasion of muscularis propria into pericolonic adipose tissue, but notthrough serosa. Arising from tubular adenoma. 156 175 III Hepatic 3.8 T3G2 Invasion through flexure mucsularis propria into subserosa/pericolicadipose, no serosal involvement. Gross configuration annular. 228 247III Rectum 5.8 T3 G2 to Invasion through G3 muscularis propria toinvolve subserosal, perirectoal adipose, and serosa 264 283 II Ascending5.5 T3 G2 Invasion through colon muscularis propria into subserosaladipose tissue. 266 285 III Transverse 9 T3 G2 Invades through colonmuscularis propria to involve pericolonic adipose, extends to serosa.268 287 I Cecum 6.5 T2 G2 Invades full thickness of muscularis propria,but mesenteric adipose free of malignancy 278 297 III Rectum 4 T3 G2Invasion into perirectal adipose tissue. 295 314 II Ascending 5.0 T3 G2Invasion through colon muscularis propria into percolic adipose tissue.296 315 III Cecum 5.5 T3 G2 Invasion through muscularis propria andinvades pericolic adipose tissue. Ileocecal junction. 339 358 IIRectosigmoid 6 T3 G2 Extends into perirectal fat but does not reachserosa 341 360 II Ascending 2 cm T3 G2 Invasion through colon invasivemuscularis propria to involve pericolonic fat. Arising from villousadenoma. 356 375 II Sigmoid 6.5 T3 G2 Through colon wall into subserosaladipose tissue. No serosal spread seen. 392 444 IV Ascending 2 T3 G2Invasion through colon muscularis propria into subserosal adiposetissue, not serosa. 393 445 II Cecum 6.0 T3 G2 Cecum, invades throughmuscularis propria to involve subserosal adipose tissue but not serosa.413 465 IV Cecum 4.8 T3 G2 Invasive through muscularis to involveperiserosal fat; abutting ileocecal junction. 517 395 IV Sigmoid 3 T3 G2penetrates muscularis propria, involves pericolonic fat. 546 565 IVAscending 5.5 T3 G2 Invasion through colon muscularis propriaextensively through submucosal and extending to serosa. 577 596 II Cecum11.5 T3 G2 Invasion through the bowel wall, into suberosal adipose.Serosal surface free of tumor. 784 803 IV Ascending 3.5 T3 G3 throughmuscularis colon propria into pericolic soft tissues 786 805 IVDescending 9.5 T3 G2 through muscularis colon propria into pericolicfat, but not at serosal surface 791 810 IV Ascending 5.8 T3 G3 Throughthe colon muscularis propria into pericolic fat 888 908 IV Ascending 2.0T2 G1 Into muscularis colon propria 889 909 IV Cecum 4.8 T3 G2 Throughmuscularis propria int subserosal tissue 890 910 IV Ascending T3 G2Through colon muscularis propria into subserosa. Lymph Reg Dist Pt LymphMet Lymph Dist Met & Met ID Met Incid Grade Loc Grade Comment  15 Pos3/8  N1 Neg MX invasive adenocarcinoma, moderately differentiated; focalperineural invasion is seen  52 Neg 0/12 N0 Neg M0 Hyperplastic polyp inappendix. 121 Neg 0/34 N0 Neg M0 Perineural invasion; donut anastomosisNeg. One tubulovillous and one tubular adenoma with no high gradedysplasia. 125 Neg 0/19 N0 Neg M0 patient history of metastatic melanoma128 Pos 1/5  N1 Neg M0 130 Pos 10/24  N2 Neg M1 133 Neg 0/9  N0 Neg M0Small separate tubular adenoma (0.4 cm) 141 Pos 7/21 N2 Pos - Liver M1Perineural invasion identified adjacent to metastatic adenocarcinoma.156 Pos 2/13 N1 Neg M0 Separate tubolovillous and tubular adenomas 228Pos 1/8  N1 Neg MX Hyperplastic polyps 264 Neg 0/10 N0 Neg M0Tubulovillous adenoma with high grade dysplasia 266 Neg 0/15 N1 Pos - MXMesenteric deposit 268 Neg 0/12 N0 Neg M0 278 Pos 7/10 N2 Neg M0Descending colon polyps, no HGD or carcinoma identified.. 295 Neg 0/12N0 Neg M0 Melanosis coli and diverticular disease. 296 Pos 2/12 N1 NegM0 Tubulovillous adenoma (2.0 cm) with no high grade dysplasia. Neg.liver biopsy. 339 Neg 0/6  N0 Neg M0 1 hyperplastic polyp identified 341Neg 0/4  N0 Neg MX 356 Neg 0/4  N0 Neg M0 392 Pos 1/6  N1 Pos - Liver M1Tumor arising at prior ileocolic surgical anastomosis. 393 Neg 0/21 N0Neg M0 413 Neg 0/7  N0 Pos - Liver M1 rediagnosis of oophorectomy pathto metastatic colon cancer. 517 Pos 6/6  N2 Neg M0 No mention of distantmet in report 546 Pos 6/12 N2 Pos - Liver M1 577 Neg 0/58 N0 Neg M0Appendix dilated and fibrotic, but not involved by tumor 784 Pos 5/17 N2Pos - Liver M1 invasive poorly differentiated adenosquamous carcinoma786 Neg 0/12 N0 Pos - Liver M1 moderately differentiated invasiveadenocarcinoma 791 Pos 13/25  N2 Pos - Liver M1 poorly differentiatedinvasive colonic adenocarcinoma 888 Pos 3/21 N0 Pos - Liver M1 well tomoderately differentiated adenocarcinomas; this patient has tumors ofthe ascending colon and the sigmoid colon 889 Pos 1/4  N1 Pos - Liver M1moderately differentiated adenocarcinoma 890 Pos 11/15  N2 Pos - LiverM1Source of Polynucleotides on Arrays

Polynucleotides for use on the arrays were obtained from both publiclyavailable sources and from cDNA libraries generated from selected celllines and patient tissues. Table 12 provides information about thepolynucleotides on the arrays including: (1) the “SEQ ID NO” assigned toeach sequence for use in the present specification; (2) the spotidentification number (“Spot ID”), an internal reference that serves asa unique identifier for the spot on the array; (3) the “Clone ID”assigned to the clone from which the sequence was isolated; (4) thenumber of the Group (“Grp”) to which the gene is assigned (see Example11 below); and (5) the gene represented by the SEQ ID NO (“Gene”).

TABLE 12 SEQ ID Spot NO ID Clone ID Grp Gene GBHit GBDesc GBScore 32233669 RG:26148:Order7TM01:C06 1 IGF2 X07868 Human DNA for insulin- 2.1E−35 like growth factor II (IGF-2); exon 7 and additional ORF 32332956 RG:240381:Order7TM20:G11 1 IGF2 X03427 Homo sapiens IGF-II 7.4E−186 gene, exon 5 324 17167 RG:730402:10010:H01 1 TTK BC000633 Homosapiens, TTK  2.1E−38 protein kinase, clone MGC: 865 IMAGE: 3343925,mRNA, complete cds 325 21711 RG:1674098:10014:H01 1 MARCKS D10522 Homosapiens mRNA for   4E−148 80K-L protein, complete cds 326 29171035JN025.C12 1 FLJ22066 AK025719 Homo sapiens cDNA: 0 FLJ22066 fis,clone HEP10611 327 30566 RG:432087:Order7TM26:D02 1 FLJ22066 AK025719Homo sapiens cDNA: 0 FLJ22066 fis, clone HEP10611 328 10638I:1644648:07B01:G04 1 NQO2 U07736 Human quinone  1.6E−171oxidoreductase2 (NQO2) gene, exon 7, complete cds 329  8491I:2594080:05A01:F01 1 FHL3 BC001351 Homo sapiens, Similar to  2.6E−34four and a half LIM domains 3, clone MGC: 8696 IMAGE: 2964682, mRNA,compl 330 27092 035Jn031.C09 1 MGC: 29604 BC019103 Homo sapiens, clone  1E−300 MGC: 29604 IMAGE: 5021401, mRNA, complete cds 331 10394I:1450639:03B02:E09 1 CETN2 BC005334 Homo sapiens, centrin,  1.1E−190EF-hand protein, 2, clone MGC: 12421 IMAGE: 3961448, mRNA, complete cds332  3295 M00008083D:D06 1 CGI-148 AF223467 Homo sapiens NPD008 2.5E−157 protein protein (NPD008) mRNA, complete cds 333 30831RG:301734:Order7TM22:H02 1 KIP2 AB012955 Homo sapiens mRNA for  5.8E−252KIP2, complete cds 334 19871 RG:196236:10006:H11 1 FGFR4 AF359246 Homosapiens fibroblast   5E−249 growth factor receptor 4 variant mRNA,complete cds 335 30858 RG:359021:Order7TM24:F02 1 BBS2 AF342736 Homosapiens BBS2   1E−100 (BBS2) mRNA, complete cds 336 17168RG:1320327:10012:H01 1 OGG1 Y11731 H. sapiens mRNA for   1E−300 DNAglycosylase 337 17487 RG:341475:10008:H01 1 MAPKAPK2 NM_032960 Homosapiens mitogen-   1E−300 activated protein kinase- activated proteinkinase 2 (MAPKAPK2), transcript variant 338 18942 RG:1895716:10015:G09 2ITAK AC007055 AC007055 Homo sapiens 3.00E−94 chromosome 14 clone BAC201F1 map 14q24.3, complete sequence 339 17365 I:504786:14A02:C07 21-8U; 1-8D; BC006794 Homo sapiens, Similar to  6.4E−295 9-27 interferoninduced transmembrane protein 3 (1-8U), clone MGC: 5225 IMAGE: 340 21144M00055353D:A04 2 1-8U; 1-8D; BC006794 Homo sapiens, Similar to  1.1E−1569-27 interferon induced transmembrane protein 3 (1-8U), clone MGC: 5225IMAGE: 341 11573 I:1513214:04A01:C11 2 BIRC3 U45878 Human inhibitor of 2.5E−157 apoptosis protein 1 mRNA, complete cds

The sequences corresponding to the SEQ ID NOS are provided in theSequence Listing.

Characterization of Sequences

The sequences of the isolated polynucleotides were first masked toeliminate low complexity sequences using the RepeatMasker maskingprogram, publicly available through a web site supported by theUniversity of Washington (See also Smit, A. F. A. and Green, P.,unpublished results). Generally, masking does not influence the finalsearch results, except to eliminate sequences of relatively littleinterest due to their low complexity, and to eliminate multiple “hits”based on similarity to repetitive regions common to multiple sequences,e.g., Alu repeats. Masking resulted in the elimination of severalsequences.

The remaining sequences of the isolated polynucleotides were used in ahomology search of the GenBank database using the TeraBLAST program(TimeLogic, Crystal Bay, Nev.), a DNA and protein sequence homologysearching algorithm. TeraBLAST is a version of the publicly availableBLAST search algorithm developed by the National Center forBiotechnology, modified to operate at an accelerated speed withincreased sensitivity on a specialized computer hardware platform. Theprogram was run with the default parameters recommended by TimeLogic toprovide the best sensitivity and speed for searching DNA and proteinsequences. Gene assignment for the query sequences was determined basedon best hit form the GenBank database; expectancy values are providedwith the hit.

Summary of TeraBLAST Search Results

Table 12 also provides information about the gene corresponding to eachpolynucleotide. Table 12 includes: (1) the “SEQ ID NO” of the sequence;(2) the GenBank Accession Number of the publicly available sequencecorresponding to the polynucleotide (“GBHit”); (3) a description of theGenBank sequence (“GBDesc”); (4) the score of the similarity of thepolynucleotide sequence and the GenBank sequence (“GBScore”). Thepublished information for each GenBank and EST description, as well asthe corresponding sequence identified by the provided accession number,are incorporated herein by reference.

Example 10 Detection of Differential Expression Using Arrays

cDNA probes were prepared from total RNA isolated from the patient cellsdescribed above. Since LCM provides for the isolation of specific celltypes to provide a substantially homogenous cell sample, this providedfor a similarly pure RNA sample.

Total RNA was first reverse transcribed into cDNA using a primercontaining a T7 RNA polymerase promoter, followed by second strand DNAsynthesis. cDNA was then transcribed in vitro to produce antisense RNAusing the T7 promoter-mediated expression (see, e.g., Luo et al. (1999)Nature Med 5:117-122), and the antisense RNA was then converted intocDNA. The second set of cDNAs were again transcribed in vitro, using theT7 promoter, to provide antisense RNA. Optionally, the RNA was againconverted into cDNA, allowing for up to a third round of T7-mediatedamplification to produce more antisense RNA. Thus the procedure providedfor two or three rounds of in vitro transcription to produce the finalRNA used for fluorescent labeling.

Fluorescent probes were generated by first adding control RNA to theantisense RNA mix, and producing fluorescently labeled cDNA from the RNAstarting material. Fluorescently labeled cDNAs prepared from the tumorRNA sample were compared to fluorescently labeled cDNAs prepared fromnormal cell RNA sample. For example, the cDNA probes from the normalcells were labeled with Cy3 fluorescent dye (green) and the cDNA probesprepared from the tumor cells were labeled with Cy5 fluorescent dye(red), and vice versa.

Each array used had an identical spatial layout and control spot set.Each microarray was divided into two areas, each area having an arraywith, on each half, twelve groupings of 32×12 spots, for a total ofabout 9,216 spots on each array. The two areas are spotted identicallywhich provide for at least two duplicates of each clone per array.

Polynucleotides for use on the arrays were obtained from both publiclyavailable sources and from cDNA libraries generated from selected celllines and patient tissues as described above and in Table 12. PCRproducts of from about 0.5 kb to 2.0 kb amplified from these sourceswere spotted onto the array using a Molecular Dynamics Gen III spotteraccording to the manufacturer's recommendations. The first row of eachof the 24 regions on the array had about 32 control spots, including 4negative control spots and 8 test polynucleotides. The testpolynucleotides were spiked into each sample before the labelingreaction with a range of concentrations from 2-600 pg/slide and ratiosof 1:1. For each array design, two slides were hybridized with the testsamples reverse-labeled in the labeling reaction. This provided forabout four duplicate measurements for each clone, two of one color andtwo of the other, for each sample.

The differential expression assay was performed by mixing equal amountsof probes from tumor cells and normal cells of the same patient. Thearrays were prehybridized by incubation for about 2 hrs at 60° C. in5×SSC/0.2% SDS/1 mM EDTA, and then washed three times in water and twicein isopropanol. Following prehybridization of the array, the probemixture was then hybridized to the array under conditions of highstringency (overnight at 42° C. in 50% formamide, 5×SSC, and 0.2% SDS.After hybridization, the array was washed at 55° C. three times asfollows: 1) first wash in 1×SSC/0.2% SDS; 2) second wash in 0.1×SSC/0.2%SDS; and 3) third wash in 0.1×SSC.

The arrays were then scanned for green and red fluorescence using aMolecular Dynamics Generation III dual color laser-scanner/detector. Theimages were processed using BioDiscovery Autogene software, and the datafrom each scan set normalized to provide for a ratio of expressionrelative to normal. Data from the microarray experiments was analyzedaccording to the algorithms described in U.S. application Ser. No.60/252,358, filed Nov. 20, 2000, by E. J. Moler, M. A. Boyle, and F. M.Randazzo, and entitled “Precision and accuracy in cDNA microarray data,”which application is specifically incorporated herein by reference.

The experiment was repeated, this time labeling the two probes with theopposite color in order to perform the assay in both “color directions.”Each experiment was sometimes repeated with two more slides (one in eachcolor direction). The level fluorescence for each sequence on the arrayexpressed as a ratio of the geometric mean of 8 replicate spots/genesfrom the four arrays or 4 replicate spots/gene from 2 arrays or someother permutation. The data were normalized using the spiked positivecontrols present in each duplicated area, and the precision of thisnormalization was included in the final determination of thesignificance of each differential. The fluorescent intensity of eachspot was also compared to the negative controls in each duplicated areato determine which spots have detected significant expression levels ineach sample.

A statistical analysis of the fluorescent intensities was applied toeach set of duplicate spots to assess the precision and significance ofeach differential measurement, resulting in a p-value testing the nullhypothesis that there is no differential in the expression level betweenthe tumor and normal samples of each patient. During initial analysis ofthe microarrays, the hypothesis was accepted if p>10⁻³, and thedifferential ratio was set to 1.000 for those spots. All other spotshave a significant difference in expression between the tumor and normalsample. If the tumor sample has detectable expression and the normaldoes not, the ratio is truncated at 1000 since the value for expressionin the normal sample would be zero, and the ratio would not be amathematically useful value (e.g., infinity). If the normal sample hasdetectable expression and the tumor does not, the ratio is truncated to0.001, since the value for expression in the tumor sample would be zeroand the ratio would not be a mathematically useful value. These lattertwo situations are referred to herein as “on/off.” Database tables werepopulated using a 95% confidence level (p>0.05).

Tables 13A-D summarize the results of the differential expressionanalysis. Table 13A-D provides: (1) the spot identification number(“Spot ID”), an internal reference that serves as a unique identifierfor the spot on the array; (2) the number of the Group (“Grp”) to whichthe gene is assigned (see Example 11 below); and (3) the ratio ofexpression of the gene in each of the patient samples, identified by thepatient ID number (e.g., 15). This data represents the ratio ofdifferential expression for the samples tested from that particularpatient's tissues (e.g., “RATIO15” is the ratio from the tissue samplesof Patient ID no. 15). The ratios of differential expression areexpressed as a normalized hybridization signal associated with the tumorprobe divided by the normalized hybridization signal with the normalprobe. Thus, a ratio greater than 1 indicates that the gene product isincreased in expression in cancerous cells relative to normal cells,while a ratio of less than 1 indicates the opposite.

TABLE 13 A: RATIO RATIO RATIO RATIO RATIO RATIO RATIO RATIO RATIO SpotID Grp Gene 015 052 121 125 128 130 133 141 156  3295 1 CGI-148 protein0.603 0.569 1.420 1.000 1.347 0.544 1.000 0.663 0.400  8491 1 FHL3 1.0001.000 10.786 6.347 4.580 2.918 5.331 1.000 2.771 10394 1 CETN2 1.0001.000 3.335 1.000 2.493 2.450 1.000 1.000 2.130 10638 1 NQO2 1.000 1.0002.522 1.720 2.495 1.000 1.748 1.000 2.018 17167 1 TTK 1.000 1.000 5.0531.000 5.484 1.000 1.000 1.000 1.000 17168 1 OGG1 1.389 1.000 1.736 1.0002.525 1.000 2.339 1.000 1.162 17487 1 MAPKAPK2 1.000 1.000 39.041 1.00026.551 1.000 54.030 0.657 0.116 19871 1 FGFR4 1.000 1.000 4.040 0.7603.246 1.000 4.017 1.859 0.224 21711 1 MARCKS 1.000 1.000 21.440 1.29410.369 1.000 20.040 1.000 1.000 27092 1 MGC:29604 1.806 2.418 5.8312.114 11.273 1.821 9.841 1.413 2.385 29171 1 FLJ22066 1.000 1.000184.016 0.728 52.758 0.849 145.030 1.000 0.015 30566 1 FLJ22066 1.0001.000 163.068 1.000 53.616 1.000 1.000 1.000 0.083 30831 1 KIP2 0.7231.000 2.349 1.000 1.972 1.000 1.000 1.437 0.626 30858 1 BBS2 1.304 0.7451.907 1.678 2.686 0.525 1.877 1.000 0.251 32956 1 IGF2 1.105 1.00020.747 1.000 10.458 1.000 1.000 1.000 0.476 33669 1 IGF2 0.592 0.38121.028 1.195 16.876 0.334 25.468 0.720 0.049 11573 2 BIRC3 1.698 2.7910.825 1.319 1.264 1.587 1.986 0.408 1.504 17365 2 1-8U; 1-8D; 9-27 3.1132.893 1.229 4.848 3.307 4.004 9.166 1.000 1.769 18942 2 ITAK 4.489 7.3861.000 6.655 4.507 5.485 12.390 1.000 2.281 21144 2 1-8U; 1-8D; 9-275.520 22.946 1.000 5.929 3.918 7.337 8.908 1.182 1.706 B: RATIO RATIORATIO RATIO RATIO RATIO RATIO RATIO RATIO Spot ID Grp Gene 228 264 266268 278 295 296 339 341  3295 1 CGI-148 protein 0.579 0.599 0.302 1.0001.270 1.000 0.484 0.561 1.000  8491 1 FHL3 1.000 1.000 1.000 12.5834.691 1000.000 1000.000 3.136 7.320 10394 1 CETN2 1.000 1.000 1.0003.463 1.000 1.000 1000.000 1.000 4.065 10638 1 NQO2 1.000 1.000 1.0003.325 1.697 1.000 1000.000 1.000 3.036 17167 1 TTK 1.000 1.724 1.5151.000 1.000 1.000 1000.000 1.000 5.355 17168 1 OGG1 1.000 1.584 1.3322.564 2.024 1.600 1.551 0.739 1.999 17487 1 MAPKAPK2 1.000 1.000 1.20643.580 23.642 2.085 1.000 0.545 18.309 19871 1 FGFR4 1.619 1.992 1.0004.407 3.989 1000.000 1.000 1.324 2.494 21711 1 MARCKS 1.000 1.000 1.19213.283 1.000 2.161 1.000 0.638 1.000 27092 1 MGC:29604 1.927 3.330 2.67810.984 9.190 4.226 8.035 0.757 14.757 29171 1 FLJ22066 1.000 1.760 1.000186.617 83.660 4.242 1000.000 0.303 102.601 30566 1 FLJ22066 1.596 1.4301.000 108.781 51.686 1.000 1.000 0.530 50.061 30831 1 KIP2 0.672 0.9521.000 1.000 2.848 1.000 1.000 1.000 2.521 30858 1 BBS2 1.393 1.547 1.4312.272 1.440 1.000 1.000 1.000 2.180 32956 1 IGF2 1.000 1.000 1.00032.991 3.788 1.000 1.000 1.565 10.202 33669 1 IGF2 0.566 0.380 0.19614.331 4.654 0.298 0.237 0.508 11.442 11573 2 BIRC3 1.000 1.645 1.0001.283 1.667 1.408 2.084 1.000 1.000 17365 2 1-8U; 1-8D; 9-27 2.633 7.2637.775 4.152 4.770 3.064 2.220 1.374 1.808 18942 2 ITAK 4.106 10.28611.733 6.840 1.000 11.385 1.000 1.892 1.690 21144 2 1-8U; 1-8D; 9-275.027 8.086 8.148 3.902 7.228 5.159 1.000 2.787 1.569 C: RATIO RATIORATIO RATIO RATIO RATIO RATIO RATIO RATIO Spot ID Grp Gene 356 392 393413 517 546 577 784 786  3295 1 CGI-148 protein 0.503 0.816 0.692 0.6490.200 1.000 1.000 0.662 0.532  8491 1 FHL3 1.000 1.000 13.185 1.0001000.000 3.131 5.278 1.000 1.000 10394 1 CETN2 1000.000 1.000 3.0151.000 1.000 1.000 1.000 1.000 1.000 10638 1 NQO2 1.000 1.000 2.850 1.0001.000 1.000 1.000 1.000 1.000 17167 1 TTK 1.000 1.000 5.355 1.000 1.0001.000 3.158 1.092 1.898 17168 1 OGG1 1.000 2.116 1.694 1.000 1.000 1.0001.672 1.701 1.000 17487 1 MAPKAPK2 1.556 51.316 43.253 0.516 1.412 0.8131.000 1.000 1.000 19871 1 FGFR4 1.000 2.284 4.041 1.000 3.005 2.1851.000 1.000 3.307 21711 1 MARCKS 1.000 32.171 26.574 0.814 1.000 1.0001.347 1.000 1.000 27092 1 MGC:29604 7.284 12.948 8.685 1.742 1.451 2.2963.357 1.329 2.919 29171 1 FLJ22066 1.000 218.198 197.610 0.330 1.6570.749 1.000 1.000 1.790 30566 1 FLJ22066 1.000 264.417 157.238 0.2931.300 1.000 1.220 2.785 1.000 30831 1 KIP2 1.000 1.997 1.964 1.000 1.3791.119 0.753 1.972 1.000 30858 1 BBS2 0.519 3.152 2.475 3.013 0.449 1.0000.662 1.339 1.000 32956 1 IGF2 1.475 25.053 23.953 1.000 1.529 1.4301.600 1.430 1.713 33669 1 IGF2 0.412 24.283 30.632 0.564 0.214 0.8530.381 0.551 0.506 11573 2 BIRC3 1.000 1.199 1.768 1.000 1.485 1.0001.429 1.000 1.648 17365 2 1-8U; 1-8D; 9-27 3.636 9.985 7.293 2.980 4.4843.107 4.362 1.645 4.670 18942 2 ITAK 12.611 16.163 7.279 3.603 6.9044.196 7.792 1.000 8.475 21144 2 1-8U; 1-8D; 9-27 10.080 18.239 8.3952.839 6.176 3.328 5.636 2.142 7.000 D: RATIO RATIO RATIO RATIO Spot IDGrp Gene 791 888 889 890  3295 1 CGI-148 protein 0.495 0.574 0.483 0.711 8491 1 FHL3 1.000 1.000 1.000 5.465 10394 1 CETN2 1.000 2.970 1.0002.848 10638 1 NQO2 1.000 1.511 1.000 2.158 17167 1 TTK 1.000 1.000 1.0002.290 17168 1 OGG1 1.000 1.000 1.000 1.519 17487 1 MAPKAPK2 1.000 1.4491.000 1.516 19871 1 FGFR4 1.000 1.988 0.646 4.007 21711 1 MARCKS 1.0001.397 1.000 1.000 27092 1 MGC:29604 3.771 1.890 2.788 1.799 29171 1FLJ22066 1.000 1.000 7.569 2.512 30566 1 FLJ22066 1.000 2.624 1.0001.713 30831 1 KIP2 1.000 1.000 1.000 4.213 30858 1 BBS2 0.749 2.3160.506 1.000 32956 1 IGF2 1.486 1.633 1.000 1.491 33669 1 IGF2 0.4740.842 2.502 0.736 11573 2 BIRC3 2.502 0.781 1.314 1.000 17365 2 1-8U;1-8D; 9-27 8.576 2.723 3.553 11.697 18942 2 ITAK 10.189 2.909 4.16511.972 21144 2 1-8U; 1-8D; 9-27 14.444 2.712 7.659 11.467

These data provide evidence that the genes represented by thepolynucleotides having the indicated sequences are differentiallyexpressed in colon cancer as compared to normal non-cancerous colontissue.

Example 11 Stratification of Colon Cancers Using Differential ExpressionData

Groups of genes with differential expression data correlating withspecific genes of interest can be identified using statistical analysissuch as the Student t-test and Spearman rank correlation (Stanton Glantz(1997) Primer of Bio-Statistics, McGraw Hill, pp 65-107, 256-262). Usingthese statistical tests, patients having tumors that exhibit similardifferential expression patterns can be assigned to Groups. At least twoGroups were identified, and are described below.

Group 1

Genes that Exhibit Differential Expression in Colon Cancer in a Patternthat Correlates with IGF2

Using both the Student-t test and the Spearman rank correlation test,the differential expression data of IGF2 correlated with that of 14distinct genes: TTK, MAPKAPK2, MARCKS, BBS2, CETN2 CGI-148 protein,FGFR4, FHL3, FLJ22066, KIP2, MGC:29604, NQO2, and OGG1 (see Tables13A-D). The differential expression data for these genes is presented ingraphical form in FIGS. 2-17. This group was identified as Group 1. IGF2is a secreted protein and has been reported to be involved in colon aswell as other cancers (Toretsky J A and Helman L J (1996) J Endocrinol149(3):367-72). Genes whose expression patterns correlate with IGF2 mayprovide a mechanism for the involvement of IGF2 in cancer. Among thegenes in Group 1 are genes such as TTK (a kinase implicated in mitoticspindle check point), MAP-KAP kinase 2 (mitogen-activated protein (MAP)kinase activated protein kinase 2), and MARCKS (myristoylatedalanine-rich C kinase substrate, which is a substrate of protein kinaseC). The protein products of these genes and their associated signalingpathways can be targets for small molecule drug development foranti-cancer therapy. Furthermore, the upregulation of IGF2 can be acriterion for selecting patients who will benefit from anti-cancertherapy targeted to the genes in Group 1 and their associated pathwaycomponents.

Group 2

Genes that Exhibit Differential Expression in Colon Cancer in a Patternthat Correlates Interferon Induced Transmembrane (IFITM) Protein Family

Using the Spearman rank correlation test, the differential expressiondata of the IFITM family (1-8U; 1-8D; 9-27) correlated with that of 2other genes: ITAK and BIRC3/H-IAP1 (see Tables 13A-D). The differentialexpression data for these genes is presented in graphical form in FIGS.18-21. This group was identified as Group 2. 1-8U/IFITM3 was previouslyreported as a gene differentially upregulated inulcerative-colitis-associated colon cancer (Hisamatsu et al (1999)Cancer Research 59, 5927-5931). Genes whose expression patternscorrelate with 1-8U/IFITM3 and its family members may provide amechanism for the involvement of inflammation in colon cancer. There areat least 3 members of the IFITM family: 9-27/IFITM1, 1-8D/IFITM2 and1-8U/IFITM3. The polynucleotides used for the detection of 1-8U/IFITM3are within a domain that is highly conserved among the 3 members.Therefore, the upregulation detected by the corresponding microarrayspots may indicate the upregulation of one or multiple members withinthe family. Among the genes in Group 2 are ITAK (IL-1, TNF alphaactivated kinase) and BIRC3/H-IAP1 (human inhibitor of apoptosis 1). Theprotein products of these genes and their associated signaling pathwayscan be targets for small molecule drug development for anti-cancertherapy. Furthermore, the upregulation of the IFITM can be a criterionfor selecting patients who will benefit from anti-cancer therapytargeted to the genes in Group 2 and their associated pathwaycomponents.

Example 12 Antisense Regulation of Gene Expression

The expression of the differentially expressed genes represented by thepolynucleotides in the cancerous cells can be analyzed using antisenseknockout technology to confirm the role and function of the gene productin tumorigenesis, e.g., in promoting a metastatic phenotype.

A number of different oligonucleotides complementary to the mRNAgenerated by the differentially expressed genes identified herein can bedesigned as potential antisense oligonucleotides, and tested for theirability to suppress expression of the genes. Sets of antisense oligomersspecific to each candidate target are designed using the sequences ofthe polynucleotides corresponding to a differentially expressed gene andthe software program HYB simulator Version 4 (available for Windows95/Windows NT or for Power Macintosh, RNAture, Inc. 1003 Health SciencesRoad, West, Irvine, Calif. 92612 USA). Factors that are considered whendesigning antisense oligonucleotides include: 1) the secondary structureof oligonucleotides; 2) the secondary structure of the target gene; 3)the specificity with no or minimum cross-hybridization to otherexpressed genes; 4) stability; 5) length and 6) terminal GC content. Theantisense oligonucleotide is designed so that it will hybridize to itstarget sequence under conditions of high stringency at physiologicaltemperatures (e.g., an optimal temperature for the cells in culture toprovide for hybridization in the cell, e.g., about 37° C.), but withminimal formation of homodimers.

Using the sets of oligomers and the HYB simulator program, three to tenantisense oligonucleotides and their reverse controls are designed andsynthesized for each candidate mRNA transcript, which transcript isobtained from the gene corresponding to the target polynucleotidesequence of interest. Once synthesized and quantitated, the oligomersare screened for efficiency of a transcript knock-out in a panel ofcancer cell lines. The efficiency of the knock-out is determined byanalyzing mRNA levels using lightcycler quantification. The oligomersthat resulted in the highest level of transcript knock-out, wherein thelevel was at least about 50%, preferably about 80-90%, up to 95% or moreup to undetectable message, are selected for use in a cell-basedproliferation assay, an anchorage independent growth assay, and anapoptosis assay.

The ability of each designed antisense oligonucleotide to inhibit geneexpression is tested through transfection into SW620 colon carcinomacells. For each transfection mixture, a carrier molecule (such as alipid, lipid derivative, lipid-like molecule, cholesterol, cholesterolderivative, or cholesterol-like molecule) is prepared to a workingconcentration of 0.5 mM in water, sonicated to yield a uniform solution,and filtered through a 0.45 μm PVDF membrane. The antisense or controloligonucleotide is then prepared to a working concentration of 100 μM insterile Millipore water. The oligonucleotide is further diluted inOptiMEM™ (Gibco/BRL), in a microfuge tube, to 2 μM, or approximately 20μg oligo/ml of OptiMEM™. In a separate microfuge tube, the carriermolecule, typically in the amount of about 1.5-2 nmol carrier/μgantisense oligonucleotide, is diluted into the same volume of OptiMEM™used to dilute the oligonucleotide. The diluted antisenseoligonucleotide is immediately added to the diluted carrier and mixed bypipetting up and down. Oligonucleotide is added to the cells to a finalconcentration of 30 nM.

The level of target mRNA that corresponds to a target gene of interestin the transfected cells is quantitated in the cancer cell lines usingthe Roche LightCycler™ real-time PCR machine. Values for the target mRNAare normalized versus an internal control (e.g., beta-actin). For each20 μl reaction, extracted RNA (generally 0.2-1 μg total) is placed intoa sterile 0.5 or 1.5 ml microcentrifuge tube, and water is added to atotal volume of 12.5 μl. To each tube is added 7.5 μl of a buffer/enzymemixture, prepared by mixing (in the order listed) 2.5 μl H₂O, 2.0 μl 10×reaction buffer, 10 μl oligo dT (20 μmol), 1.0 μl dNTP mix (10 mM each),0.5 μl RNAsin® (20 u) (Ambion, Inc., Hialeah, Fla.), and 0.5 μl MMLVreverse transcriptase (50 u) (Ambion, Inc.). The contents are mixed bypipetting up and down, and the reaction mixture is incubated at 42° C.for 1 hour. The contents of each tube are centrifuged prior toamplification.

An amplification mixture is prepared by mixing in the following order:1×PCR buffer II, 3 mM MgCl₂, 140 μM each dNTP, 0.175 μmol each oligo,1:50,000 dil of SYBR® Green, 0.25 mg/ml BSA, 1 unit Taq polymerase, andH₂O to 20 μl. (PCR buffer II is available in 10× concentration fromPerkin-Elmer, Norwalk, Conn.). In 1× concentration it contains 10 mMTris pH 8.3 and 50 mM KCl. SYBR® Green (Molecular Probes, Eugene, Oreg.)is a dye which fluoresces when bound to double stranded DNA. As doublestranded PCR product is produced during amplification, the fluorescencefrom SYBR® Green increases. To each 20 μl aliquot of amplificationmixture, 2 μl of template RT is added, and amplification is carried outaccording to standard protocols. The results are expressed as thepercent decrease in expression of the corresponding gene productrelative to non-transfected cells, vehicle-only transfected(mock-transfected) cells, or cells transfected with reverse controloligonucleotides.

Example 13 Effect of Expression on Proliferation

The effect of gene expression on the inhibition of cell proliferationcan be assessed in metastatic breast cancer cell lines (MDA-MB-231(“231”)); SW620 colon colorectal carcinoma cells; SKOV3 cells (a humanovarian carcinoma cell line); or LNCaP, PC3, 22Rv1, MDA-PCA-2b, or DU145prostate cancer cells.

Cells are plated to approximately 60-80% confluency in 96-well dishes.Antisense or reverse control oligonucleotide is diluted to 2 μM inOptiMEM™. The oligonucleotide-OptiMEM™ can then be added to a deliveryvehicle, which delivery vehicle can be selected so as to be optimizedfor the particular cell type to be used in the assay. The oligo/deliveryvehicle mixture is then further diluted into medium with serum on thecells. The final concentration of oligonucleotide for all experimentscan be about 300 nM.

Antisense oligonucleotides are prepared as described above (see Example12). Cells are transfected overnight at 37° C. and the transfectionmixture is replaced with fresh medium the next morning. Transfection iscarried out as described above in Example 12.

Those antisense oligonucleotides that result in inhibition ofproliferation of SW620 cells indicate that the corresponding gene playsa role in production or maintenance of the cancerous phenotype incancerous colon cells. Those antisense oligonucleotides that inhibitproliferation in SKOV3 cells represent genes that play a role inproduction or maintenance of the cancerous phenotype in cancerous breastcells. Those antisense oligonucleotides that result in inhibition ofproliferation of MDA-MB-231 cells indicate that the corresponding geneplays a role in production or maintenance of the cancerous phenotype incancerous ovarian cells. Those antisense oligonucleotides that inhibitproliferation in LNCaP, PC3, 22Rv1, MDA-PCA-2b, or DU145 cells representgenes that play a role in production or maintenance of the cancerousphenotype in cancerous prostate cells.

Example 14 Effect of Gene Expression on Cell Migration

The effect of gene expression on the inhibition of cell migration can beassessed in SW620 colon cancer cells using static endothelial cellbinding assays, non-static endothelial cell binding assays, andtransmigration assays.

For the static endothelial cell binding assay, antisenseoligonucleotides are prepared as described above (see Example 12). Twodays prior to use, colon cancer cells (CaP) are plated and transfectedwith antisense oligonucleotide as described above (see Examples 4 and5). On the day before use, the medium is replaced with fresh medium, andon the day of use, the medium is replaced with fresh medium containing 2μM CellTracker green CMFDA (Molecular Probes, Inc.) and cells areincubated for 30 min. Following incubation, CaP medium is replaced withfresh medium (no CMFDA) and cells are incubated for an additional 30-60min. CaP cells are detached using CMF PBS/2.5 mM EDTA or trypsin, spunand resuspended in DMEM/1% BSA/10 mM HEPES pH 7.0. Finally, CaP cellsare counted and resuspended at a concentration of 1×10⁶ cells/ml.

Endothelial cells (EC) are plated onto 96-well plates at 40-50%confluence 3 days prior to use. On the day of use, EC are washed 1× withPBS and 50 k DMDM/1% BSA/10 mM HEPES pH 7 is added to each well. To eachwell is then added 50K (50□) CaP cells in DMEM/1% BSA/10 mM HEPES pH 7.The plates are incubated for an additional 30 min and washed 5× with PBScontaining Ca⁺⁺ and Mg⁺⁺. After the final wash, 100 μL PBS is added toeach well and fluorescence is read on a fluorescent plate reader(Ab492/Em 516 nm).

For the non-static endothelial cell binding assay, CaP are prepared asdescribed above. EC are plated onto 24-well plates at 30-40% confluence3 days prior to use. On the day of use, a subset of EC are treated withcytokine for 6 hours then washed 2× with PBS. To each well is then added150-200K CaP cells in DMEM/1% BSA/10 mM HEPES pH 7. Plates are placed ona rotating shaker (70 RPM) for 30 min and then washed 3× with PBScontaining Ca⁺⁺ and Mg⁺⁺. After the final wash, 500 μL PBS is added toeach well and fluorescence is read on a fluorescent plate reader(Ab492/Em 516 nm).

For the transmigration assay, CaP are prepared as described above withthe following changes. On the day of use, CaP medium is replaced withfresh medium containing 5 μM CellTracker green CMFDA (Molecular Probes,Inc.) and cells are incubated for 30 min. Following incubation, CaPmedium is replaced with fresh medium (no CMFDA) and cells are incubatedfor an additional 30-60 min. CaP cells are detached using CMF PBS/2.5 mMEDTA or trypsin, spun and resuspended in EGM-2-MV medium. Finally, CaPcells are counted and resuspended at a concentration of 1×10⁶ cells/ml.

EC are plated onto FluorBlok transwells (BD Biosciences) at 30-40%confluence 5-7 days before use. Medium is replaced with fresh medium 3days before use and on the day of use. To each transwell is then added50K labeled CaP. 30 min prior to the first fluorescence reading, 10 μgof FITC-dextran (10K MW) is added to the EC plated filter. Fluorescenceis then read at multiple time points on a fluorescent plate reader(Ab492/Em 516 nm).

Those antisense oligonucleotides that result in inhibition of binding ofSW620 colon cancer cells to endothelial cells indicate that thecorresponding gene plays a role in the production or maintenance of thecancerous phenotype in cancerous colon cells. Those antisenseoligonucleotides that result in inhibition of endothelial celltransmigration by SW620 colon cancer cells indicate that thecorresponding gene plays a role in the production or maintenance of thecancerous phenotype in cancerous colon cells.

Example 15 Effect of Gene Expression on Colony Formation

The effect of gene expression upon colony formation of SW620 cells,SKOV3 cells, MD-MBA-231 cells, LNCaP cells, PC3 cells, 22Rv1 cells,MDA-PCA-2b cells, and DU145 cells can be tested in a soft agar assay.Soft agar assays are conducted by first establishing a bottom layer of 2ml of 0.6% agar in media plated fresh within a few hours of layering onthe cells. The cell layer is formed on the bottom layer by removingcells transfected as described above from plates using 0.05% trypsin andwashing twice in media. The cells are counted in a Coulter counter, andresuspended to 10⁶ per ml in media. 10 μl aliquots are placed with mediain 96-well plates (to check counting with WST1), or diluted further forthe soft agar assay. 2000 cells are plated in 800 μl 0.4% agar induplicate wells above 0.6% agar bottom layer. After the cell layer agarsolidifies, 2 ml of media is dribbled on top and antisense or reversecontrol oligo (produced as described in Example 12) is added withoutdelivery vehicles. Fresh media and oligos are added every 3-4 days.Colonies form in 10 days to 3 weeks. Fields of colonies are counted byeye. Wst-1 metabolism values can be used to compensate for smalldifferences in starting cell number. Larger fields can be scanned forvisual record of differences.

Those antisense oligonucleotides that result in inhibition of colonyformation of SW620 cells indicate that the corresponding gene plays arole in production or maintenance of the cancerous phenotype incancerous colon cells. Those antisense oligonucleotides that inhibitcolony formation in SKOV3 cells represent genes that play a role inproduction or maintenance of the cancerous phenotype in cancerous breastcells. Those antisense oligonucleotides that result in inhibition ofcolony formation of MDA-MB-231 cells indicate that the correspondinggene plays a role in production or maintenance of the cancerousphenotype in cancerous ovarian cells. Those antisense oligonucleotidesthat inhibit colony formation in LNCaP, PC3, 22Rv1, MDA-PCA-2b, or DU145cells represent genes that play a role in production or maintenance ofthe cancerous phenotype in cancerous prostate cells.

Example 16 Induction of Cell Death Upon Depletion of Polypeptides byDepletion of mRNA (“Antisense Knockout”)

In order to assess the effect of depletion of a target message upon celldeath, SW620 cells, or other cells derived from a cancer of interest,can be transfected for proliferation assays. For cytotoxic effect in thepresence of cisplatin (cis), the same protocol is followed but cells areleft in the presence of 2 μM drug. Each day, cytotoxicity is monitoredby measuring the amount of LDH enzyme released in the medium due tomembrane damage. The activity of LDH is measured using the CytotoxicityDetection Kit from Roche Molecular Biochemicals. The data is provided asa ratio of LDH released in the medium vs. the total LDH present in thewell at the same time point and treatment (rLDH/tLDH). A positivecontrol using antisense and reverse control oligonucleotides for BCL2 (aknown anti-apoptotic gene) is included; loss of message for BCL2 leadsto an increase in cell death compared with treatment with the controloligonucleotide (background cytotoxicity due to transfection).

Example 17 Functional Analysis of Gene Products Differentially Expressedin Colon Cancer in Patients

The gene products of sequences of a gene differentially expressed incancerous cells can be further analyzed to confirm the role and functionof the gene product in tumorigenesis, e.g., in promoting or inhibitingdevelopment of a metastatic phenotype. For example, the function of geneproducts corresponding to genes identified herein can be assessed byblocking function of the gene products in the cell. For example, wherethe gene product is secreted or associated with a cell surface membrane,blocking antibodies can be generated and added to cells to examine theeffect upon the cell phenotype in the context of, for example, thetransformation of the cell to a cancerous, particularly a metastatic,phenotype. In order to generate antibodies, a clone corresponding to aselected gene product is selected, and a sequence that represents apartial or complete coding sequence is obtained. The resulting clone isexpressed, the polypeptide produced isolated, and antibodies generated.The antibodies are then combined with cells and the effect upontumorigenesis assessed.

Where the gene product of the differentially expressed genes identifiedherein exhibits sequence homology to a protein of known function (e.g.,to a specific kinase or protease) and/or to a protein family of knownfunction (e.g., contains a domain or other consensus sequence present ina protease family or in a kinase family), then the role of the geneproduct in tumorigenesis, as well as the activity of the gene product,can be examined using small molecules that inhibit or enhance functionof the corresponding protein or protein family.

Additional functional assays include, but are not necessarily limitedto, those that analyze the effect of expression of the correspondinggene upon cell cycle and cell migration. Methods for performing suchassays are well known in the art.

Example 18 Contig Assembly and Additional Gene Characterization

The sequences of the polynucleotides provided in the present inventioncan be used to extend the sequence information of the gene to which thepolynucleotides correspond (e.g., a gene, or mRNA encoded by the gene,having a sequence of the polynucleotide described herein). This expandedsequence information can in turn be used to further characterize thecorresponding gene, which in turn provides additional information aboutthe nature of the gene product (e.g., the normal function of the geneproduct). The additional information can serve to provide additionalevidence of the gene product's use as a therapeutic target, and providefurther guidance as to the types of agents that can modulate itsactivity.

In one example, a contig is assembled using a sequence of apolynucleotide of the present invention, which is present in a clone. A“contig” is a contiguous sequence of nucleotides that is assembled fromnucleic acid sequences having overlapping (e.g., shared or substantiallysimilar) sequence information. The sequences of publicly-available ESTs(Expressed Sequence Tags) and the sequences of various clones fromseveral cDNA libraries synthesized at Chiron can be used in the contigassembly.

The contig is assembled using the software program Sequencher, version4.05, according to the manufacturer's instructions and an overviewalignment of the contiged sequences is produced. The sequenceinformation obtained in the contig assembly can then be used to obtain aconsensus sequence derived from the contig using the Sequencher program.The consensus sequence is used as a query sequence in a TeraBLASTNsearch of the DGTI DoubleTwist Gene Index (DoubleTwist, Inc., Oakland,Calif.), which contains all the EST and non-redundant sequence in publicdatabases.

Through contig assembly and the use of homology searching softwareprograms, the sequence information provided herein can be readilyextended to confirm, or confirm a predicted, gene having the sequence ofthe polynucleotides described in the present invention. Further theinformation obtained can be used to identify the function of the geneproduct of the gene corresponding to the polynucleotides describedherein. While not necessary to the practice of the invention,identification of the function of the corresponding gene, can provideguidance in the design of therapeutics that target the gene to modulateits activity and modulate the cancerous phenotype (e.g., inhibitmetastasis, proliferation, and the like).

Example 19 Source of Biological Materials

The biological materials used in the experiments that led to the presentinvention are described below.

Source of Patient Tissue Samples

Normal and cancerous tissues were collected from patients using lasercapture microdissection (LCM) techniques, which techniques are wellknown in the art (see, e.g., Ohyama et al. (2000) Biotechniques29:530-6; Curran et al. (2000) Mol. Pathol. 53:64-8; Suarez-Quian et al.(1999) Biotechniques 26:328-35; Simone et al. (1998) Trends Genet.14:272-6; Conia et al. (1997) J. Clin. Lab. Anal. 11:28-38; Emmert-Bucket al. (1996) Science 274:9981001). Table 14 below provides informationabout each patient from which the prostate tissue samples were isolated,including: 1) the “Patient ID”, which is a number assigned to thepatient for identification purposes; 2) the “Tissue Type”; and 3) the“Gleason Grade” of the tumor. Histopathology of all primary tumorsindicated the tumor was adenocarcinoma.

TABLE 14 Prostate patient data. Gleason Patient ID Tissue Type Grade 93Prostate Cancer 3 + 4 94 Prostate Cancer 3 + 3 95 Prostate Cancer 3 + 396 Prostate Cancer 3 + 3 97 Prostate Cancer 3 + 2 100 Prostate Cancer3 + 3 101 Prostate Cancer 3 + 3 104 Prostate Cancer 3 + 3 105 ProstateCancer 3 + 4 106 Prostate Cancer 3 + 3 138 Prostate Cancer 3 + 3 151Prostate Cancer 3 + 3 153 Prostate Cancer 3 + 3 155 Prostate Cancer 4 +3 171 Prostate Cancer 3 + 4 173 Prostate Cancer 3 + 4 231 ProstateCancer 3 + 4 232 Prostate Cancer 3 + 3 251 Prostate Cancer 3 + 4 282Prostate Cancer 4 + 3 286 Prostate Cancer 3 + 3 294 Prostate Cancer 3 +4 351 Prostate Cancer 5 + 4 361 Prostate Cancer 3 + 3 362 ProstateCancer 3 + 3 365 Prostate Cancer 3 + 2 368 Prostate Cancer 3 + 3 379Prostate Cancer 3 + 4 388 Prostate Cancer 5 + 3 391 Prostate Cancer 3 +3 420 Prostate Cancer 3 + 3 425 Prostate Cancer 3 + 3 428 ProstateCancer 4 + 3 431 Prostate Cancer 3 + 4 492 Prostate Cancer 3 + 3 493Prostate Cancer 3 + 4 496 Prostate Cancer 3 + 3 510 Prostate Cancer 3 +3 511 Prostate Cancer 4 + 3 514 Prostate Cancer 3 + 3 549 ProstateCancer 3 + 3 552 Prostate Cancer 3 + 3 858 Prostate Cancer 3 + 4 859Prostate Cancer 3 + 4 864 Prostate Cancer 3 + 4 883 Prostate Cancer 4 +4 895 Prostate Cancer 3 + 3 901 Prostate Cancer 3 + 3 909 ProstateCancer 3 + 3 921 Prostate Cancer 3 + 3 923 Prostate Cancer 4 + 3 934Prostate Cancer 3 + 3 1134 Prostate Cancer 3 + 4 1135 Prostate Cancer3 + 3 1136 Prostate Cancer 3 + 4 1137 Prostate Cancer 3 + 3 1138Prostate Cancer 4 + 3

Source of Polynucleotides on Arrays

Polynucleotides for use on the arrays were obtained from both publiclyavailable sources and from cDNA libraries generated from selected celllines and patient tissues. Table 15 provides information about thepolynucleotides on the arrays including: 1) the “SEQ ID NO” assigned toeach sequence for use in the present specification; 2) the spotidentification number (“Spot ID”), an internal reference that serves asa unique identifier for the spot on the array; 3) the “Sequence Name”assigned to each sequence; and 4) the “Sample Name or Clone Name”assigned to the sample or clone from which the sequence was isolated.The sequences corresponding to the SEQ ID NOS are provided in theSequence Listing.

Characterization of Sequences

The sequences of the isolated polynucleotides were first masked toeliminate low complexity sequences using the RepeatMasker maskingprogram, publicly available through a web site supported by theUniversity of Washington (See also Smit, A. F. A. and Green, P.,unpublished results). Generally, masking does not influence the finalsearch results, except to eliminate sequences of relative littleinterest due to their low complexity, and to eliminate multiple “hits”based on similarity to repetitive regions common to multiple sequences,e.g., Alu repeats. Masking resulted in the elimination of severalsequences.

The remaining sequences of the isolated polynucleotides were used in ahomology search of the GenBank database using the TeraBLAST program(TimeLogic, Crystal Bay, Nev.), a DNA and protein sequence homologysearching algorithm. TeraBLAST is a version of the publicly availableBLAST search algorithm developed by the National Center forBiotechnology, modified to operate at an accelerated speed withincreased sensitivity on a specialized computer hardware platform. Theprogram was run with the default parameters recommended by TimeLogic toprovide the best sensitivity and speed for searching DNA and proteinsequences. Gene assignment for the query sequences was determined basedon best hit form the GenBank database; expectancy values are providedwith the hit.

Tables 16 and 17 provide information about the gene corresponding toeach polynucleotide. Tables 16 and 17 include: 1) the spotidentification number (“Spot ID”); 2) the GenBank Accession Number ofthe publicly available sequence corresponding to the polynucleotide(“GenBankHit”); 3) a description of the GenBank sequence(“GenBankDesc”); and 4) the score of the similarity of thepolynucleotide sequence and the GenBank sequence (“GenBankScore”). Thepublished information for each GenBank and EST description, as well asthe corresponding sequence identified by the provided accession number,are incorporated herein by reference.

Example 20 Detection of Differential Expression Using Arrays

cDNA probes were prepared from total RNA isolated from the patient cellsdescribed above. Since LCM provides for the isolation of specific celltypes to provide a substantially homogenous cell sample, this providedfor a similarly pure RNA sample.

Total RNA was first reverse transcribed into cDNA using a primercontaining a T7 RNA polymerase promoter, followed by second strand DNAsynthesis. cDNA was then transcribed in vitro to produce antisense RNAusing the T7 promoter-mediated expression (see, e.g., Luo et al. (1999)Nature Med 5:117-122), and the antisense RNA was then converted intocDNA. The second set of cDNAs were again transcribed in vitro, using theT7 promoter, to provide antisense RNA. Optionally, the RNA was againconverted into cDNA, allowing for up to a third round of T7-mediatedamplification to produce more antisense RNA. Thus the procedure providedfor two or three rounds of in vitro transcription to produce the finalRNA used for fluorescent labeling.

Fluorescent probes were generated by first adding control RNA to theantisense RNA mix, and producing fluorescently labeled cDNA from the RNAstarting material. Fluorescently labeled cDNAs prepared from the tumorRNA sample were compared to fluorescently labeled cDNAs prepared fromnormal cell RNA sample. For example, the cDNA probes from the normalcells were labeled with Cy3 fluorescent dye (green) and the cDNA probesprepared from the tumor cells were labeled with Cy5 fluorescent dye(red), and vice versa.

Each array used had an identical spatial layout and control spot set.Each microarray was divided into two areas, each area having an arraywith, on each half, twelve groupings of 32×12 spots, for a total ofabout 9,216 spots on each array. The two areas are spotted identicallywhich provide for at least two duplicates of each clone per array.

Polynucleotides for use on the arrays were obtained from both publiclyavailable sources and from cDNA libraries generated from selected celllines and patient tissues as described above and in Table 15. PCRproducts of from about 0.5 kb to 2.0 kb amplified from these sourceswere spotted onto the array using a Molecular Dynamics Gen III spotteraccording to the manufacturer's recommendations. The first row of eachof the 24 regions on the array had about 32 control spots, including 4negative control spots and 8 test polynucleotides. The testpolynucleotides were spiked into each sample before the labelingreaction with a range of concentrations from 2-600 pg/slide and ratiosof 1:1. For each array design, two slides were hybridized with the testsamples reverse-labeled in the labeling reaction. This provided forabout four duplicate measurements for each clone, two of one color andtwo of the other, for each sample.

The differential expression assay was performed by mixing equal amountsof probes from tumor cells and normal cells of the same patient. Thearrays were prehybridized by incubation for about 2 hrs at 60° C. in5×SSC/0.2% SDS/1 mM EDTA, and then washed three times in water and twicein isopropanol. Following prehybridization of the array, the probemixture was then hybridized to the array under conditions of highstringency (overnight at 42° C. in 50% formamide, 5×SSC, and 0.2% SDS.After hybridization, the array was washed at 55° C. three times asfollows: 1) first wash in 1×SSC/0.2% SDS; 2) second wash in 0.1×SSC/0.2%SDS; and 3) third wash in 0.1×SSC.

The arrays were then scanned for green and red fluorescence using aMolecular Dynamics Generation III dual color laser-scanner/detector. Theimages were processed using BioDiscovery Autogene software, and the datafrom each scan set normalized to provide for a ratio of expressionrelative to normal. Data from the microarray experiments was analyzedaccording to the algorithms described in U.S. application Ser. No.60/252,358, filed Nov. 20, 2000, by E. J. Moler, M. A. Boyle, and F. M.Randazzo, and entitled “Precision and accuracy in cDNA microarray data,”which application is specifically incorporated herein by reference.

The experiment was repeated, this time labeling the two probes with theopposite color in order to perform the assay in both “color directions.”Each experiment was sometimes repeated with two more slides (one in eachcolor direction). The level fluorescence for each sequence on the arrayexpressed as a ratio of the geometric mean of 8 replicate spots/genesfrom the four arrays or 4 replicate spots/gene from 2 arrays or someother permutation. The data were normalized using the spiked positivecontrols present in each duplicated area, and the precision of thisnormalization was included in the final determination of thesignificance of each differential. The fluorescent intensity of eachspot was also compared to the negative controls in each duplicated areato determine which spots have detected significant expression levels ineach sample.

A statistical analysis of the fluorescent intensities was applied toeach set of duplicate spots to assess the precision and significance ofeach differential measurement, resulting in a p-value testing the nullhypothesis that there is no differential in the expression level betweenthe tumor and normal samples of each patient. During initial analysis ofthe microarrays, the hypothesis was accepted if p>10⁻³, and thedifferential ratio was set to 1.000 for those spots. All other spotshave a significant difference in expression between the tumor and normalsample. If the tumor sample has detectable expression and the normaldoes not, the ratio is truncated at 1000 since the value for expressionin the normal sample would be zero, and the ratio would not be amathematically useful value (e.g., infinity). If the normal sample hasdetectable expression and the tumor does not, the ratio is truncated to0.001, since the value for expression in the tumor sample would be zeroand the ratio would not be a mathematically useful value. These lattertwo situations are referred to herein as “on/off.” Database tables werepopulated using a 95% confidence level (p>0.05).

TABLE 15 SEQ ID Spot NO Id Sequence Name Sample Name or Clone Name 342987 gbH13036.1 NIH50_43563 343 1016 019.G8.sp6_128478 M00006968D:E03 3441019 1chip1.K15.T7HSQ3_328869 M00005636D:B08 345 1033RTA00000184AR.p.16.1 M00001568C:D03 346 1047 122.B4.sp6_132088M00001655C:E04 347 1049 324.E8.sp6_145687 M00001657A:C02 348 1494chip1.F13.SP6_329984 M00001470A:C06 349 260 HX2105-6 2105-6 350 279gbR51346.1 NIH50_39093 351 283 gbH05914.1 NIH50_43550 352 3151chip1.K13.T7HSQ3_328837 M00005629C:E09 353 320 1chip1.P13.T7HSQ3_328842M00006964D:C05 354 342 626.C7.sp6_157434 M00007965A:C03 355 369 SL178m13SL178 356 403 RTA00000848F.c.07.1 M00023298C:E11 357 4533chip1.F02.T7HSQ3_329424 M00008050A:D12 358 46040000063.F01.T7HSQ3_332264 M00022135A:C04 359 462 642.G1.sp6_156335M00022137A:A05 360 507 RTA00000603F.b.03.1 M00004163D:A08 361 511774.H7.sp6_162527 M00004167D:H05 362 515 627.B2.sp6_157609M00007976D:D10 363 530 636.A2.sp6_158173 M00022004A:F05 364 578271.A1.sp6_145248 M00001429A:G04 365 579 269.B1.sp6_144876M00001358B:F05 366 582 271.C1.sp6_145272 M00001429C:C03 367 589269.G1.sp6_144936 M00001360C:B05 368 596 271.B7.sp6_145266M00001445D:D07 369 605 6chip1.N13.SP6_330760 M00001374D:D10 370 6278chip1.C14.Topo2_336359 2016-5 371 635 HX2058-2 2058-2 372 637 HX2090-12090-1 373 641 1chip1.A02.T7HSQ3_328651 M00006600A:E02 374 653RTA00000321F.e.05.1 M00006619A:C04 375 656 959.SP6.H01_180102M00007082B:D06 376 688 RTA00001082F.m.03.1 M00027211C:F06 377 742660.C2.sp6_159543 M00026921D:F12 378 760 6chip1.G15.SP6_330785M00026961D:G06 379 764 RTA00001069F.i.01.1 M00026962D:E01 380 770021.A2.sp6_128760 M00005467A:G06 381 784 021.H2.sp6_128844M00007007A:H06 382 789 5chip1.E16.SP6_330415 M00001393B:B01 383 81640000062.H02.T7HSQ3_332178 M00008095B:G07 384 828 634.F8.sp6_155946M00021638B:F03 385 866 RTA22200231F.p.10.1.P M00008002B:G03 386 920656.D8.sp6_159369 M00026896A:C09 387 929 919.A2.SP6_168666M00001339C:G05 388 964 HX2106-1 2106-1 389 978 HX2103-1 2103-1 390 10618chip1.E03.Topo2_336185 SL141 391 1108 661.B8.sp6_159729 M00027116A:A10392 1111 RTA00001069F.b.02.1 M00023302D:E10 393 1117 653.G8.sp6_159021M00023305A:C02 394 1137 022.A6.sp6_128956 M00007943C:f02 395 1145019.G8.sp6_128478 M00006968D:e03 396 1176 642.D8.sp6_156306M00022180D:E11 397 1195 5chip1.K03.SP6_330213 M00001675B:G05 398 1251RTA00001038F.a.21.1 M00023413D:F04 399 1261 655.G2.sp6_156528M00023419C:B06 400 1266 RTA00000922F.g.12.1 M00026900D:F02 401 1282271.A2.sp6_145249 M00001430D:H07 402 1283 6chip1.D03.SP6_330590M00001360D:H10 403 1298 RTA00000585F.o.09.2 M00001448A:C04 404 1307269.F8.sp6_144931 M00001378D:E03 405 1309 269.G8.sp6_144943M00001378D:G05 406 1310 271.G8.sp6_145327 M00001451D:F01 407 1319HX2030-2 2030-2 408 1323 8chip1.K04.Topo2_336207 2054-2 409 1325HX2076-5 2076-5 410 1331 HX2017-1 2017-1 411 1341 HX2090-3 2090-3 4121351 1chip1.G04.T7HSQ3_328689 M00006630A:D01 413 1466RTA00000852F.h.21.1 M00026964B:H10 414 1506 40000062.A03.T7HSQ3_332179M00008095C:A10 415 1524 40000062.B09.T7HSQ3_332228 M00021649B:F09 4161607 323.D3.sp6_145478 M00001497A:A09 417 1644 020.A2.sp6_128592M00001393B:B01 418 1645 919.G3.SP6_168739 M00001342C:C01 419 1659268.F9.sp6_144740 M00001350B:D10 420 1663 919.H9.SP6_168757M00001350C:C05 421 1664 270.H9.sp6_145148 M00001411A:G02 422 1689gbR61053.1 NIH50_42096 423 1693 gbH16957.1 NIH50_50117 424 17231chip1.K17.T7HSQ3_328901 M00005694A:A09 425 1752 626.D9.sp6_157448M00007967D:G06 426 1767 SL149m13 SL149 427 1769 8chip1.I05.Topo2_336221SL150 428 1789 8chip1.M17.Topo2_336417 SL200 429 1791 SL201m13 SL201 4301794 661.A3.sp6_159712 M00027028A:A06 431 1807 653.H3.sp6_159028M00023285D:C05 432 1810 RTA00001069F.k.22.1 M00027143D:E10 433 18521chip1.L18.T7HSQ3_328918 M00005380A:E11 434 18593chip1.D06.T7HSQ3_329486 M00008057A:B01 435 1868 642.F3.sp6_156325M00022151A:B12 436 1895 RTA22200222F.k.17.1.P M00004069B:G01 437 1899RTA00000603F.a.21.1 M00004072D:E08 438 1927 RTA22200231F.l.22.1.PM00007985A:B08 439 1936 RTA00000854F.g.12.1 M00008020C:H09 440 1955655.B3.sp6_156469 M00023423B:A04 441 1957 655.C3.sp6_156481M00023424C:A01 442 1992 271.D3.sp6_145286 M00001434D:F08 443 2000271.H3.sp6_145334 M00001435C:F08 444 2014 4chip1.M17.SP6_330055M00001462A:E06 445 2028 8chip1.L06.Topo2_336240 2237-3 446 20308chip1.N06.Topo2_336242 2245-1 447 2067 1chip1.C18.T7HSQ3_328909M00006715C:C09 448 2108 RTA00001083F.e.05.1 M00027619D:A06 449 2110RTA00001083F.e.06.1 M00027622D:H04 450 2137 sl102t7 SL102 451 2139sl103m13 SL103 452 2152 RTA22200241F.k.11.1.P M00026931B:E12 453 2190021.G4.sp6_128834 M00006953B:C05 454 2237 3chip1.N19.T7HSQ3_329704M00007943D:B09 455 2267 773.F10.sp6_162349 M00001573D:H09 456 2280RTA00001206F.a.07.1 M00008023B:A05 457 2338 270.A4.sp6_145059M00001394C:B12 458 2357 268.C10.sp6_144705 M00001351A:A01 459 2375gbR35294.1 NIH50_37451 460 2381 gbH09589.1 NIH50_46171 461 2427RTA00001064F.k.13.2 M00005767D:B03 462 2442 626.E4.sp6_157455M00007960A:D12 463 2513 653.A10.sp6_158951 M00023312D:F10 464 2514661.A10.sp6_159719 M00027168A:E01 465 2528 661.H10.sp6_159803M00027176D:B08 466 2549 019.E10.sp6_128456 M00005645D:g06 467 2557020.G4.sp6_128666 M00005404C:f02 468 2564 RTA22200232F.o.21.1.PM00022154C:D08 469 2568 642.D4.sp6_156302 M00022158D:C11 470 2588642.F10.sp6_156332 M00022208D:B02 471 2605 774.G4.sp6_162502M00004085C:C02 472 2613 774.C10.sp6_162546 M00004243D:C01 473 2621RTA00000193AR.c.15.2 M00004248B:E08 474 2629 RTA22200231F.m.13.1.PM00007987B:F11 475 2632 RTA22200233F.c.14.1.P M00008025D:A02 476 2662RTA00001069F.c.03.1 M00023363C:A04 477 2663 RTA00000786F.o.16.3M00023431C:F07 478 2694 271.C4.sp6_145275 M00001436B:E11 479 2696271.D4.sp6_145287 M00001436C:C03 480 2702 271.G4.sp6_145323M00001437B:B08 481 2716 271.F10.sp6_145317 M00001468A:D02 482 27288chip1.H08.Topo2_336268 2208-5 483 2732 HX2237-4 2237-4 484 2734HX2245-2 2245-2 485 2736 HX2254-2 2254-2 486 2751 HX2100-1 2100-1 4872765 955.SP6.G04_177960 M00006653C:B09 488 2766 RTA22200230F.g.19.1.PM00007154B:H08 489 2791 RTA00000789F.g.11.1 M00003994A:G12 490 2837sl108m13 SL108 491 2919 625.D5.sp6_155727 M00007936A:C09 492 2922959.SP6.G09_180098 M00008100B:G11 493 2977 RTA22200231F.m.16.1.PM00007990D:A11 494 2979 RTA22200231F.m.20.1.P M00007992A:D02 495 2988628.F9.sp6_157856 M00008039A:C09 496 3009 323.A5.sp6_145444M00001503C:D01 497 3090 HX2104-3 2104-3 498 3091 gbR42581.1 NIH50_31143499 3093 gbR45594.1 NIH50_35483 500 3097 gbR61295.1 NIH50_42352 501 3099gbH05820.1 NIH50_44255 502 3101 gbH16908.1 NIH50_50666 503 3122019.G10.sp6_128480 M00007019A:B01 504 3143 324.D5.sp6_145672M00001605D:C02 505 3152 626.H5.sp6_157492 M00007963B:B04 506 3235019.D5.sp6_128439 M00005443D:b03 507 3275 633.F5.sp6_156135M00008072D:E12 508 3284 642.B11.sp6_156285 M00022211D:A02 509 33015chip1.E09.SP6_330303 M00003820A:G06 510 3317 774.C11.sp6_162554M00004282B:D11 511 3346 636.A10.sp6_158181 M00022068C:F05 512 3372RTA00000854F.m.01.1 M00023395C:F06 513 3394 271.A5.sp6_145252M00001437D:E12 514 3396 271.B5.sp6_145264 M00001438A:B09 515 3419269.F11.sp6_144934 M00001387A:A08 516 3440 HX2254-4 2254-4 517 3453HX2093-3 2093-3 518 3455 HX2100-2 2100-2 519 3469 RTA00002902F.h.07.1.PM00006678A:A03 520 3517 RTA22200224F.j.03.1.P M00005358D:A11 521 3531SL66t7 SL66 522 3575 654.D12.sp6_159181 M00023398C:D01 523 3683RTA00000717F.o.13.1 M00007994C:F08 524 3710 RTA22200232F.i.18.1.PM00022074D:H11 525 3712 636.H11.sp6_158266 M00022075A:B09 526 3745268.A6.sp6_144677 M00001344D:H07 527 3760 013717 M00001405B:A11 528 3772270.F12.sp6_145127 M00001427D:G03 529 3776 270.H12.sp6_145151M00001428C:A07 530 3785 gbR58991.1 NIH50_41452 531 3794 HX2105-1 2105-1532 3831 1chip1.G23.T7HSQ3_328993 M00006582A:D11 533 4007RTA22200222F.m.10.1.P M00004136A:D10 534 4019 774.B12.sp6_162561M00004331A:A03 535 4037 RTA22200231F.o.10.1.P M00007996C:F04 536 4068344.B6.sp6_146241 M00023397B:E08 537 4100 4chip1.C11.SP6_329949M00001441A:A09 538 4107 920.F6.SP6_168826 M00001372A:D01 539 4123019.A4.sp6_128402 M00001389A:F09 540 4124 4chip1.K23.SP6_330149M00001481C:A12 541 4127 6chip1.P23.SP6_330922 M00001389C:G01 542 41284chip1.O23.SP6_330153 M00001482D:D11 543 4135 HX2032-2 2032-2 544 4157HX2093-5 2093-5 545 4193 RTA00002895F.h.23.1.P M00004087B:E02 546 84542231168 I:2231168:08B01:C01 547 8486 1813269 I:1813269:05B01:C01 5488509 1732092 I:1732092:05A01:G07 549 8513 Incyte3.A01.T3pINCY_352048I:3325119:07A01:A01 550 8537 Incyte3.I13.T3pINCY_352248I:3176222:07A01:E07 551 8546 Incyte2.B01.T3pINCY_351665I:1705208:06B01:A01 552 8549 Incyte2.E01.T3pINCY_351668I:1623214:06A01:C01 553 8568 Incyte2.H13.T3pINCY_351863I:1712888:06B01:D07 554 8569 Incyte2.I13.T3pINCY_351864I:1702752:06A01:E07 555 8570 1696224 I:1696224:06B01:E07 556 8599Incyte5.H13.T3pINCY_353015 I:1678926:11A01:D07 557 8608 3676190I:3676190:11B01:H07 558 8634 Incyt14.I13.T3pINCY_377264I:1439934:03B01:E07 559 8637 1640555 I:1640555:03A01:G07 560 8644Incyt12.C01.T3pINCY_368180 I:2171743:01B01:B01 561 8672 2885982I:2885982:01B01:H07 562 8703 2917169 I:2917169:12A01:H07 563 87302477854 I:2477854:10B01:E07 564 8743 1858905 I:1858905:04A01:D01 5658829 2950228 I:2950228:08A02:G07 566 8835 1732335 I:1732335:05A02:B01567 8856 I1.H14.T3pINCY1_343720 I:1803418:05B02:D07 568 8858I1.J14.T3pINCY1_343722 I:1857652:05B02:E07 569 8860I1.L14.T3pINCY1_343724 I:1568725:05B02:F07 570 8862I1.N14.T3pINCY1_343726 I:1687060:05B02:G07 571 8890 3044552I:3044552:07B02:E07 572 8945 Incyte5.B14.T3pINCY_353025I:3282436:11A02:A07 573 8959 1817388 I:1817388:11A02:H07 574 8960Incyt10.O14.T3pINCY_367632 I:2488216:11B02:H07 575 8996Incyt11.D02.T3pINCY_367813 I:2365149:01B02:B01 576 9008Incyte8.P01.T3pINCY_354174 I:3211615:01B02:H01 577 9013Incyte8.E14.T3pINCY_354371 I:1419396:01A02:C07 578 9021Incyt11.N13.T3pINCY_367999 I:2862971:01A02:G07 579 9055Incyte6.P13.T3pINCY_353598 I:4335824:12A02:H07 580 9082 3275493I:3275493:10B02:E07 581 9097 2021576 I:2021576:04A02:E01 582 9110Incyt14.F14.T3pINCY_377277 I:2989411:04B02:C07 583 9111I1.G14.T3pINCY1_343719 I:1958902:04A02:D07 584 9143 2728590I:2728590:02A02:D07 585 9168 Incyte4.O03.T3pINCY_352478I:2344817:08B01:H02 586 9171 Incyte3.D16.T3pINCY_352291I:3236109:08A01:B08 587 9186 1574890 I:1574890:05B01:A02 588 91911421929 I:1421929:05A01:D02 589 9201 3142736 I:3142736:05A01:A08 5909278 Incyte2.N15.T3pINCY_351901 I:1305950:06B01:G08 591 9296Incyt10.O03.T3pINCY_367456 I:1804548:11B01:H02 592 9300Incyt10.C15.T3pINCY_367636 I:3053958:11B01:B08 593 9312Incyt10.O15.T3pINCY_367648 I:2799347:11B01:H08 594 9318Incyt14.E03.T3pINCY_377100 I:1312824:03B01:C02 595 9348 2745048I:2745048:01B01:B02 596 9364 2683564 I:2683564:01B01:B08 597 9366Incyt12.E15.T3pINCY_368406 I:2725511:01B01:C08 598 9368Incyte8.H16.T3pINCY_354406 I:2233375:01B01:D08 599 9381Incyt10.F03.T3pINCY_367447 I:3218334:12A01:C02 600 9442I1.B03.T3pINCY1_343538 I:1636639:04B01:A02 601 9448I1.H03.T3pINCY1_343544 I:2455617:04B01:D02 602 9456I1.P03.T3pINCY1_343552 I:2806166:04B01:H02 603 9472I1.P15.T3pINCY1_343744 I:2510171:04B01:H08 604 9487Incyt12.O04.T3pINCY_368240 I:2190284:02A01:H02 605 9499Incyte7.K15.T3pINCY_354009 I:1861971:02A01:F08 606 9501 3360454I:3360454:02A01:G08 607 9512 2948256 I:2948256:08B02:D02 608 95272045705 I:2045705:08A02:D08 609 9528 2544622 I:2544622:08B02:D08 6109540 1522716 I:1522716:05B02:B02 611 9552 I1.P04.T3pINCY1_343568I:1820522:05B02:H02 612 9553 2365295 I:2365295:05A02:A08 613 9560I1.H16.T3pINCY1_343752 I:1822577:05B02:D08 614 9574 2472778I:2472778:07B02:C02 615 9596 3141918 I:3141918:07B02:F08 616 96181306814 I:1306814:06B02:A08 617 9624 Incyte2.H16.T3pINCY_351911I:3034694:06B02:D08 618 9640 Incyt10.G04.T3pINCY_367464I:2859033:11B02:D02 619 9645 Incyte5.N04.T3pINCY_352877I:2795249:11A02:G02 620 9647 Incyte5.P04.T3pINCY_352879I:2966535:11A02:H02 621 9649 Incyte5.B16.T3pINCY_353057I:1483713:11A02:A08 622 9666 Incyt14.A04.T3pINCY_377112I:1453049:03B02:A02 623 9678 Incyt14.M04.T3pINCY_377124I:1415990:03B02:G02 624 9687 Incyte9.G15.T3pINCY_354773I:2992851:03A02:D08 625 9697 Incyt11.B03.T3pINCY_367827I:1477568:01A02:A02 626 9698 2779637 I:2779637:01B02:A02 627 9716Incyt11.D16.T3pINCY_368037 I:2786575:01B02:B08 628 9720Incyt11.H16.T3pINCY_368041 I:2455118:01B02:D08 629 9722Incyt11.J16.T3pINCY_368043 I:2840251:01B02:E08 630 9739 2902903I:2902903:12A02:F02 631 9741 Incyte6.N03.T3pINCY_353436I:3126828:12A02:G02 632 9755 3126622 I:3126622:12A02:F08 633 9770Incyte5.I04.T3pINCY_352872 I:2911347:10B02:E02 634 9884Incyte4.K17.T3pINCY_352698 I:2908878:08B01:F09 635 9889 2639181I:2639181:05A01:A03 636 9901 3132987 I:3132987:05A01:G03 637 99113139163 I:3139163:05A01:D09 638 9913 2242817 I:2242817:05A01:E09 6399914 1904751 I:1904751:05B01:E09 640 9916 1750553 I:1750553:05B01:F09641 9920 1888940 I:1888940:05B01:H09 642 9949 Incyte3.M17.T3pINCY_352316I:3970665:07A01:G09 643 9952 Incyte3.P17.T3pINCY_352319I:1633393:07B01:H09 644 9956 Incyte2.D05.T3pINCY_351731I:1617326:06B01:B03 645 9981 Incyte2.M17.T3pINCY_351932I:1720149:06A01:G09 646 9989 Incyte5.F05.T3pINCY_352885I:2689747:11A01:C03 647 9995 Incyte5.L05.T3pINCY_352891I:2367733:11A01:F03 648 10003 1850531 I:1850531:11A01:B09 649 10012Incyt10.K17.T3pINCY_367676 I:2594407:11B01:F09 650 10020Incyt14.C05.T3pINCY_377130 I:1406786:03B01:B03 651 10021 1930235I:1930235:03A01:C03 652 10035 I1.C17.T3pINCY1_343763 I:1526240:03A01:B09653 10046 Incyt14.M17.T3pINCY_377332 I:1510714:03B01:G09 654 10047I1.O17.T3pINCY1_343775 I:2952864:03A01:H09 655 10083 2922292I:2922292:12A01:B03 656 10103 Incyte6.G18.T3pINCY_353669I:3714075:12A01:D09 657 10153 Incyt14.J05.T3pINCY_377137I:1712592:04A01:E03 658 10160 I1.P05.T3pINCY1_343584 I:2696735:04B01:H03659 10200 Incyte7.H17.T3pINCY_354038 I:1702266:02B01:D09 660 102311808121 I:1808121:08A02:D09 661 10243 Incyt15.C05.T3pINCY_377526I:3070110:05A02:B03 662 10257 Incyt15.A17.T3pINCY_377716I:2860815:05A02:A09 663 10285 Incyte3.M06.T3pINCY_352140I:1930135:07A02:G03 664 10301 2669174 I:2669174:07A02:G09 665 10334Incyte2.N18.T3pINCY_351949 I:3354893:06B02:G09 666 10355Incyte5.D18.T3pINCY_353091 I:4215852:11A02:B09 667 10366Incyt10.M18.T3pINCY_367694 I:2896792:11B02:G09 668 10374Incyt14.E06.T3pINCY_377148 I:1513989:03B02:C03 669 10388Incyt14.C18.T3pINCY_377338 I:1453450:03B02:B09 670 10463Incyte6.P17.T3pINCY_353662 I:4592475:12A02:H09 671 10481Incyte5.A17.T3pINCY_353072 I:1726307:10A02:A09 672 10508Incyt14.L06.T3pINCY_377155 I:1900378:04B02:F03 673 10519 1655492I:1655492:04A02:D09 674 10569 Incyte3.J08.T3pINCY_352169I:2447969:08A01:E04 675 10594 1871362 I:1871362:05B01:A04 676 106011337615 I:1337615:05A01:E04 677 10650 Incyte3.J19.T3pINCY_352345I:2456393:07B01:E10 678 10674 Incyte2.B19.T3pINCY_351953I:1911622:06B01:A10 679 10684 4082816 I:4082816:06B01:F10 680 10686Incyte2.N19.T3pINCY_351965 I:1450849:06B01:G10 681 10746Incyt14.I19.T3pINCY_377360 I:1445895:03B01:E10 682 10762Incyte8.J08.T3pINCY_354280 I:2852042:01B01:E04 683 10766 2071761I:2071761:01B01:G04 684 10767 Incyt11.O08.T3pINCY_367920I:1336836:01A01:H04 685 10777 2591814 I:2591814:01A01:E10 686 10801Incyt10.B19.T3pINCY_367699 I:3951088:12A01:A10 687 10805Incyt10.F19.T3pINCY_367703 I:3815547:12A01:C10 688 10815Incyte6.O20.T3pINCY_353709 I:2881469:12A01:H10 689 10830 1438966I:1438966:10B01:G04 690 10832 2174773 I:2174773:10B01:H04 691 108552555828 I:2555828:04A01:D04 692 10864 I1.P07.T3pINCY1_343616I:2966620:04B01:H04 693 10870 I1.F19.T3pINCY1_343798 I:2832889:04B01:C10694 10873 Incyt14.J19.T3pINCY_377361 I:1342493:04A01:E10 695 109211675571 I:1675571:08A02:E04 696 10924 1349433 I:1349433:08B02:F04 69710925 1819282 I:1819282:08A02:G04 698 10936 1709017 I:1709017:08B02:D10699 10937 3121962 I:3121962:08A02:E10 700 10938 3409027I:3409027:08B02:E10 701 10941 1697490 I:1697490:08A02:G10 702 10961Incyt15.A19.T3pINCY_377748 I:3176845:05A02:A10 703 10997Incyte3.E20.T3pINCY_352356 I:3495906:07A02:C10 704 11035 1630804I:1630804:06A02:F10 705 11050 Incyte6.I07.T3pINCY_353495I:2494284:11B02:E04 706 11053 Incyte5.N08.T3pINCY_352941I:3316536:11A02:G04 707 11057 Incyte5.B20.T3pINCY_353121I:3743802:11A02:A10 708 11092 Incyt14.C20.T3pINCY_377370I:1690653:03B02:B10 709 11100 Incyt14.K20.T3pINCY_377378I:1636553:03B02:F10 710 11104 Incyt14.O20.T3pINCY_377382I:1402228:03B02:H10 711 11112 Incyte8.H07.T3pINCY_354262I:2918558:01B02:D04 712 11114 Incyt11.J08.T3pINCY_367915I:2837773:01B02:E04 713 11149 Incyt10.N08.T3pINCY_367535I:4049957:12A02:G04 714 11153 Incyt10.B20.T3pINCY_367715I:2182353:12A02:A10 715 11201 2579602 I:2579602:04A02:A04 716 112022824181 I:2824181:04B02:A04 717 11208 2842835 I:2842835:04B02:D04 71811221 1958560 I:1958560:04A02:C10 719 11223 I1.G20.T3pINCY1_343815I:1749417:04A02:D10 720 11231 2495131 I:2495131:04A02:H10 721 112692133481 I:2133481:08A01:C05 722 11290 Incyte4.I21.T3pINCY_352760I:1340424:08B01:E11 723 11322 1858171 I:1858171:05B01:E11 724 11335Incyte3.G09.T3pINCY_352182 I:3360365:07A01:D05 725 11341Incyte3.M09.T3pINCY_352188 I:1453445:07A01:G05 726 11347Incyte3.C21.T3pINCY_352370 I:3334367:07A01:B11 727 11351Incyte3.G21.T3pINCY_352374 I:3002566:07A01:D11 728 11380 1701809I:1701809:06B01:B11 729 11396 Incyt10.C09.T3pINCY_367540I:2796468:11B01:B05 730 11463 Incyt11.G10.T3pINCY_367944I:1486087:01A01:D05 731 11473 Incyt11.A22.T3pINCY_368130I:2555034:01A01:A11 732 11485 Incyt11.M22.T3pINCY_368142I:1402967:01A01:G11 733 11489 Incyt10.B09.T3pINCY_367539I:2884153:12A01:A05 734 11493 2608167 I:2608167:12A01:C05 735 11543Incyte4.H22.T3pINCY_352775 I:2821541:10A01:D11 736 11568I1.P09.T3pINCY1_343648 I:2883195:04B01:H05 737 11569Incyt14.B21.T3pINCY_377385 I:1509602:04A01:A11 738 11583Incyt14.P21.T3pINCY_377399 I:2832224:04A01:H11 739 11624 2343403I:2343403:08B02:D05 740 11639 1880426 I:1880426:08A02:D11 741 116751511342 I:1511342:05A02:F11 742 11677 1805745 I:1805745:05A02:G11 74311682 2707290 I:2707290:07B02:A05 744 11683 3872557 I:3872557:07A02:B05745 11731 Incyte2.C22.T3pINCY_352002 I:1689068:06A02:B11 746 117363511355 I:3511355:06B02:D11 747 11739 Incyte2.K22.T3pINCY_352010I:1699587:06A02:F11 748 11745 3097582 I:3097582:11A02:A05 749 11794Incyt14.A22.T3pINCY_377400 I:2949427:03B02:A11 750 11806Incyt14.M22.T3pINCY_377412 I:1525881:03B02:G11 751 11819 2158884I:2158884:01A02:F05 752 11835 Incyt11.L21.T3pINCY_368125I:2183580:01A02:F11 753 11836 Incyt11.L22.T3pINCY_368141I:1806769:01B02:F11 754 11855 Incyt10.P10.T3pINCY_367569I:3856893:12A02:H05 755 11928 Incyt14.H22.T3pINCY_377407I:1683944:04B02:D11 756 11934 Incyt14.N22.T3pINCY_377413I:1907952:04B02:G11 757 11945 Incyte7.I10.T3pINCY_353927I:1817352:02A02:E05 758 11992 Incyte4.G23.T3pINCY_352790I:1683245:08B01:D12 759 12025 3176179 I:3176179:05A01:E12 760 12035Incyte3.C11.T3pINCY_352210 I:3175507:07A01:B06 761 12098 3553751I:3553751:11B01:A06 762 12187 Incyt11.K24.T3pINCY_368172I:1504554:01A01:F12 763 12201 Incyte6.I12.T3pINCY_353575I:2957410:12A01:E06 764 12253 1725001 I:1725001:10A01:G12 765 12258I1.B11.T3pINCY1_343666 I:2989991:04B01:A06 766 12259Incyt14.D11.T3pINCY_377227 I:1514989:04A01:B06 767 12283Incyt14.L23.T3pINCY_377427 I:1481225:04A01:F12 768 12295Incyte7.G11.T3pINCY_353941 I:1624459:02A01:D06 769 12298Incyte7.J11.T3pINCY_353944 I:2122820:02B01:E06 770 12329 2591352I:2591352:08A02:E06 771 12332 2551421 I:2551421:08B02:F06 772 12369Incyt15.A23.T3pINCY_377812 I:1252255:05A02:A12 773 12388 2674482I:2674482:07B02:B06 774 12446 Incyte2.N24.T3pINCY_352045I:1634046:06B02:G12 775 12499 Incyte9.C23.T3pINCY_354897I:2513883:03A02:B12 776 12515 Incyt11.D11.T3pINCY_367957I:2537805:01A02:B06 777 12540 Incyte8.L23.T3pINCY_354522I:1730527:01B02:F12 778 12544 Incyt11.P24.T3pINCY_368177I:1733522:01B02:H12 779 12546 3948420 I:3948420:12B01:A06 780 125483679736 I:3679736:12B01:B06 781 12555 Incyte6.L11.T3pINCY_353562I:4083705:12A02:F06 782 16846 772853 I:772853:19A01:D07 783 168812028093 I:2028093:15A01:E07 784 16883 2132508 I:2132508:15A01:F07 78516917 Incyte20.I02.Alpha2_380275 I:3144018:18B01:E01 786 16935Incyte20.K14.Alpha2_380469 I:1967531:18B01:F07 787 16959 1426031I:1426031:14B01:B07 788 17017 1001970 I:1001970:14A01:E07 789 17049K1.I14.Laf3_324935 RG:160664:10006:E07 790 17090 341491I:341491:13B01:A01 791 17119 2058935 I:2058935:13A01:H07 792 17122AA858434 RG:1420946:10004:A01 793 17143 R51346 NIH50_39093 794 17236Incyte4.C14.T3pINCY_352642 I:1602726:09B01:B07 795 17365 504786I:504786:14A02:C07 796 17370 2103752 I:2103752:14B02:E07 797 17377K1.B01.Laf3_324720 RG:197713:10007:A01 798 17379 K1.D01.Laf3_324722RG:205212:10007:B01 799 17386 AI523571 RG:2117694:10016:E01 800 17395K1.D13.Laf3_324914 RG:207395:10007:B07 801 17398 AI421409RG:2097257:10016:C07 802 17422 Incyte18.N01.Alpha2_379490I:349535:16B02:G01 803 17432 Incyte18.H13.Alpha2_379676I:1965049:16B02:D07 804 17454 1995971 I:1995971:13B02:G01 805 174572132815 I:2132815:13A02:A07 806 17475 N44546 RG:272992:10008:B01 80717479 W03193 RG:296383:10008:D01 808 17496 H08652 RG:45089:10005:D07 80917511 K1.H02.Laf3_324742 RG:1409220:10013:D01 810 17524K2.C13.Laf3_325298 RG:1705470:10015:B07 811 17603 1001730I:1001730:15A01:B02 812 17609 1922531 I:1922531:15A01:E02 813 17618707667 I:707667:15B01:A08 814 17726 1997233 I:1997233:14B01:G08 81517730 AA128438 RG:526536:10002:A02 816 17746 AA070046RG:530002:10002:A08 817 17756 AA197021 RG:608953:10002:F08 818 177932054420 I:2054420:13A01:A02 819 17795 1994472 I:1994472:13A01:B02 82017851 H13036 NIH50_43563 821 17854 R18972 RG:33368:10004:G08 822 17867AA281116 RG:711647:10010:F02 823 17878 K1.E15.Laf3_324947RG:1047592:10012:C08 824 18006 Incyte21.F16.Alpha2_380880I:2760114:19B02:C08 825 18062 2307314 I:2307314:14B02:G02 826 180691981145 I:1981145:14A02:C08 827 18097 R99405 RG:201268:10007:A08 82818178 R20998 RG:36399:10005:A02 829 18187 W24158 RG:310019:10008:F02 83018235 AA923101 RG:1521317:10013:F08 831 18305 743595 I:743595:15A01:A03832 18311 2621547 I:2621547:15A01:D03 833 18314 1988412I:1988412:15B01:E03 834 18316 1987738 I:1987738:15B01:F03 835 183211922944 I:1922944:15A01:A09 836 18323 1213932 I:1213932:15A01:B09 83718362 2296027 I:2296027:19B01:E09 838 18431 1998269 I:1998269:14A01:H09839 18445 R85309 RG:180296:10006:G03 840 18447 H30045RG:190269:10006:H03 841 18454 AA131155 RG:587068:10002:C09 842 18460AA167493 RG:609044:10002:F09 843 18464 AA197125 RG:629241:10002:H09 84418471 Incyte21.G06.Alpha2_380721 I:1953051:16A01:D03 845 18473Incyte21.I06.Alpha2_380723 I:518826:16A01:E03 846 18519 1997703I:1997703:13A01:D09 847 18560 R14989 RG:35716:10004:H09 848 18571K2.L05.Laf3_325179 RG:712070:10010:F03 849 18594Incyte19.A06.Alpha2_379947 I:1997779:17B01:A03 850 18620Incyte19.K18.Alpha2_380149 I:1998428:17B01:F09 851 18624Incyte19.O18.Alpha2_380153 I:406788:17B01:H09 852 18665 1968413I:1968413:15A02:E03 853 18683 552654 I:552654:15A02:F09 854 18687 637576I:637576:15A02:H09 855 18693 Incyte20.F06.Alpha2_380336I:606875:19A02:C03 856 18724 1962095 I:1962095:18B02:B03 857 18758856900 I:856900:14B02:C03 858 18760 2132752 I:2132752:14B02:D03 85918769 143987 I:143987:14A02:A09 860 18787 K1.D05.Laf3_324786RG:206694:10007:B03 861 18797 N23769 RG:263708:10007:G03 862 18821Incyte18.E05.Alpha2_379545 I:1461515:16A02:C03 863 18845Incyte18.M17.Alpha2_379745 I:1425861:16A02:G09 864 18860 700559I:700559:13B02:F03 865 18872 1844755 I:1844755:13B02:D09 866 18891W30991 RG:310347:10008:F03 867 18894 H19237 RG:51009:10005:G03 868 18919K1.H06.Laf3_324806 RG:1415437:10013:D03 869 18920 K2.G05.Laf3_325174RG:1734353:10015:D03 870 18926 AI281021 RG:1872251:10015:G03 871 18937K1.J18.Laf3_325000 RG:1476452:10013:E09 872 18942 K2.M17.Laf3_325372RG:1895716:10015:G09 873 18988 Incyte4.L05.T3pINCY_352507I:2069305:09B02:F03 874 19005 2674167 I:2674167:09A02:G09 875 190252296518 I:2296518:15A01:A10 876 19113 692827 I:692827:14A01:E04 87719130 1998594 I:1998594:14B01:E10 878 19166 AA186459 RG:625691:10002:G10879 19173 Incyte21.E08.Alpha2_380751 I:293495:16A01:C04 880 191833187911 I:3187911:16A01:H04 881 19219 406016 I:406016:13A01:B10 88219227 671776 I:671776:13A01:F10 883 19259 H06516 NIH50_44180 884 19287AA290719 RG:700320:10010:D10 885 19348 Incyte4.C20.T3pINCY_352738I:2556708:09B01:B10 886 19370 136571 I:136571:15B02:E04 887 19376Incyte18.O08.Alpha2_379603 I:1988674:15B02:H04 888 19389 556016I:556016:15A02:G10 889 19401 483757 I:483757:19A02:E04 890 19444 1923893I:1923893:18B02:B10 891 19473 130254 I:130254:14A02:A10 892 194822263936 I:2263936:14B02:E10 893 19506 AI335696 RG:1949583:10016:A10 89419512 AI523861 RG:2116699:10016:D10 895 19517 K1.N19.Laf3_325020RG:266649:10007:G10 896 19527 996772 I:996772:16A02:D04 897 19574 635178I:635178:13B02:C10 898 19600 T83145 RG:110764:10005:H04 899 19636K2.C19.Laf3_325394 RG:1706414:10015:B10 900 19641 K1.J20.Laf3_325032RG:1476433:10013:E10 901 19667 Incyte19.C19.Alpha2_380157I:1368834:17A02:B10 902 19684 Incyte4.D07.T3pINCY_352531I:2680168:09B02:B04 903 19701 1515905 I:1515905:09A02:C10 904 19713996104 I:996104:15A01:A05 905 19725 1966446 I:1966446:15A01:G05 90619738 1999120 I:1999120:15B01:E11 907 19743 591358 I:591358:15A01:H11908 19835 2055926 I:2055926:14A01:F11 909 19887Incyte21.O10.Alpha2_380793 I:452536:16A01:H05 910 19907 2056035I:2056035:13A01:B05 911 19922 2102320 I:2102320:13B01:A11 912 19946R38438 RG:26394:10004:E05 913 19955 R42581 NIH50_31143 914 19996AA745592 RG:1283072:10012:F11 915 20084 Incyte18.C22.Alpha2_379815I:79576:15B02:B11 916 20170 1431632 I:1431632:14B02:E05 917 20171 234123I:234123:14A02:F05 918 20184 2027012 I:2027012:14B02:D11 919 20185128997 I:128997:14A02:E11 920 20209 K1.B21.Laf3_325040RG:204966:10007:A11 921 20212 AI377014 RG:2065950:10016:B11 922 202621995380 I:1995380:13B02:C05 923 20302 H19394 RG:51505:10005:G05 92420331 K1.L10.Laf3_324874 RG:1519327:10013:F05 925 20401 1824332I:1824332:09A02:A11 926 20422 735149 I:735149:15B01:C06 927 204361530218 I:1530218:15B01:B12 928 20508 1963854 I:1963854:18B01:F12 92920530 167371 I:167371:14B01:A12 930 20551 K1.G12.Laf3_324901RG:151093:10006:D06 931 20554 AA143470 RG:591811:10002:E06 932 20557R87294 RG:180978:10006:G06 933 20558 AA187806 RG:624431:10002:G06 93420570 AA159912 RG:593090:10002:E12 935 20587 Incyte21.K12.Alpha2_380821I:2303180:16A01:F06 936 20617 911015 I:911015:13A01:E06 937 206241968576 I:1968576:13B01:H06 938 20676 K1.C11.Laf3_324881RG:967302:10012:B06 939 20696 AA627319 RG:1157566:10012:D12 940 20714Incyte19.I12.Alpha2_380051 I:1943853:17B01:E06 941 20716 1218621I:1218621:17B01:F06 942 20799 1967095 I:1967095:15A02:H12 943 20878998612 I:998612:14B02:G06 944 20892 699410 I:699410:14B02:F12 945 20937Incyte18.I11.Alpha2_379645 I:429577:16A02:E06 946 20939Incyte18.K11.Alpha2_379647 I:2117221:16A02:F06 947 20976 1782172I:1782172:13B02:H06 948 20986 1986809 I:1986809:13B02:E12 949 209901986550 I:1986550:13B02:G12 950 20999 W07144 RG:300017:10008:D06 95121029 AA890655 RG:1405692:10013:C06 952 21035 K1.L12.Laf3_324906RG:1519656:10013:F06 953 21038 AI268327 RG:1880845:10015:G06 954 21050K2.I23.Laf3_325464 RG:1841029:10015:E12 955 21189 RTA22200010F.e.10.1.PM00056386D:H12 956 21212 1.L13.Beta5_309680 M00056193B:C11 957 212141.N13.Beta5_309682 M00056193B:D06 958 21234 4.B13.Beta5_310822M00054882C:C06 959 21245 4.M13.Beta5_310833 M00054680B:D06 960 21290RTA00002690F.a.18.2.P M00042437B:G03 961 21307 RTA22200001F.g.08.1.PM00042702D:B02 962 21339 RTA22200011F.f.10.1.P M00056569A:B12 963 21345W79308 RG:346944:10009:A01 964 21349 K2.E02.Laf3_325124RG:376801:10009:C01 965 21391 RTA22200016F.o.05.1.P M00057273B:H10 96621407 RTA22200017F.e.08.1.P M00057336A:C12 967 21539 1.C02.Beta5_309495M00055932A:C02 968 21543 1.G02.Beta5_309499 M00055935D:B06 969 215462.J01.Beta5_309870 M00056908D:D08 970 21568 2.P13.Beta5_310068M00056952B:C08 971 21569 4.A02.Beta5_310645 M00054728C:E03 972 215754.G02.Beta5_310651 M00054730D:F06 973 21650 RTA22200009F.o.15.1.PM00042867B:F03 974 21654 RTA22200009F.o.18.1.P M00042868A:A06 975 21658RTA22200009F.p.01.1.P M00042869D:B09 976 21660 RTA22200009F.p.01.1.PM00042869D:B09 977 21671 2.G01.Beta5_309867 M00056719C:G03 978 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534.L21.beta5_568084M00073753C:A02 2366 36960 534.P21.beta5_568088 M00073754B:D03 2367 369632504.P01.GZ43_366150 M00072977D:F11 2368 36966 530.F09.beta5_565902M00074230C:F02 2369 36967 2504.P17.GZ43_366166 M00072978B:C07 2370 369762458.A21.GZ43_356629 M00074231C:G02 2371 36989 2505.H18.GZ43_366359M00073012C:C08 2372 36990 530.N21.beta5_566102 M00074256A:D06 2373 36999533.G09.beta5_567119 M00074958A:E09 2374 37011 533.C21.beta5_567307M00072951D:B02 2375 37017 533.I21.beta5_567313 M00072953C:G08 2376 370182506.N09.GZ43_366878 M00073869C:A02 2377 37023 2467.I24.GZ43_360681M00072981D:F06 2378 37027 537.C09.beta5_569803 M00073594A:C01 2379 37035537.K09.beta5_569811 M00073595A:A10 2380 37046 537.F21.beta5_569998M00074290C:B05 2381 37049 2536.E11.GZ43_370578 M00073616A:F06 2382 370532536.E23.GZ43_370590 M00073617B:F03 2383 37054 2459.H03.GZ43_357163M00074293B:H08 2384 37056 537.P21.beta5_570008 M00074293C:G09 2385 37062529.F10.beta5_565534 M00074131A:H09 2386 37065 529.I10.beta5_565537M00074014B:C11 2387 37072 529.P10.beta5_565544 M00074132C:F10 2388 37073529.A22.beta5_565721 M00074026C:C06 2389 37085 2558.M22.GZ43_374621M00074027D:G03 2390 37087 529.O22.beta5_565735 M00074028C:C04 2391 37088529.P22.beta5_565736 M00074156B:E07 2392 37103 2457.E24.GZ43_356332M00074206A:H12 2393 37108 2560.O19.GZ43_375434 M00074102C:E01 2394 37109527.E22.beta5_564957 M00074218C:B12 2395 37125 536.F09.beta5_569038M00074535D:H03 2396 37130 2456.G16.GZ43_355988 M00074172C:D05 2397 37136536.O09.beta5_569047 M00074174A:C02 2398 37144 536.G21.beta5_569231M00074191B:B05 2399 37146 2456.O10.GZ43_356174 M00074191C:D08 2400 37149536.N21.beta5_569238 M00074561D:D12 2401 37152 536.O21.beta5_569239M00074192C:C10 2402 37162 2368.C09.GZ43_346435 M00073512B:E12 2403 37172535.D22.beta5_568860 M00073530B:A02 2404 37176 535.H22.beta5_568864M00073531B:H02 2405 37215 532.O22.beta5_566951 M00074906C:H07 2406 37218531.B10.beta5_566362 M00074310D:B04 2407 37220 531.D10.beta5_566364M00074310D:D02 2408 37243 2482.N14.GZ43_359597 M00074730D:F06 2409 372482464.F24.GZ43_357824 M00074839D:A04 2410 37315 530.C10.beta5_565915M00073768B:D10 2411 37322 530.J10.beta5_565922 M00075425C:G02 2412 373242498.K17.GZ43_365108 M00075454D:A11 2413 37330 530.B22.beta5_566106M00075498C:B11 2414 37336 2507.L15.GZ43_367220 M00075501A:F10 2415 373462491.O22.GZ43_363954 M00075231D:D09 2416 37379 537.C10.beta5_569819M00074916C:H10 2417 37381 537.E10.beta5_569821 M00074916D:B12 2418 37397537.E22.beta5_570013 M00074930B:D04 2419 37398 537.F22.beta5_570014M00074774A:D03 2420 37401 2466.H22.GZ43_360271 M00074932A:F01 2421 37431529.G23.beta5_565743 M00074001D:G02 2422 37433 529.I23.beta5_565745M00074002A:D11 2423 37434 529.J23.beta5_565746 M00074869D:D08 2424 37437529.M23.beta5_565749 M00074002B:E10 2425 37438 529.N23.beta5_565750M00074870B:C05 2426 37447 527.G11.beta5_564783 M00073808C:H06 2427 37457527.A23.beta5_564969 M00073819A:A12 2428 37467 527.K23.beta5_564979M00073819C:F05 2429 37469 527.M23.beta5_564981 M00073819D:A05 2430 374792367.H19.GZ43_346181 M00073468A:G03 2431 37510 2541.L10.GZ43_372665M00073838C:F02 2432 37522 2506.C08.GZ43_366613 M00073850A:H09 2433 375282506.C14.GZ43_366619 M00073850D:A03 2434 37532 535.L23.beta5_568884M00073851A:C04 2435 37551 532.O11.beta5_566775 M00075165D:B06 2436 375612491.I06.GZ43_363794 M00075203A:G06 2437 37575 531.G11.beta5_566383M00074473B:A09 2438 37579 531.K11.beta5_566387 M00074474D:F08 2439 37581531.M11.beta5_566389 M00074476A:A06 2440 37584 531.P11.beta5_566392M00074441B:A02 2441 37591 2474.P14.GZ43_361991 M00074514A:E08 2442 37592531.H23.beta5_566576 M00074425C:E05 2443 37595 531.K23.beta5_566579M00074515A:E02 2444 37597 531.M23.beta5_566581 M00074515A:G08 2445 37637534.E11.beta5_567917 M00073884A:D12 2446 37638 534.F11.beta5_567918M00073735C:E04 2447 37660 534.L23.beta5_568116 M00073757A:G10 2448 37662534.N23.beta5_568118 M00073757C:B09 2449 37667 2505.A09.GZ43_366182M00072979C:F02 2450 37677 530.M11.beta5_565941 M00072980B:C06 2451 376802458.C03.GZ43_356659 M00074234B:B05 2452 37682 2458.L01.GZ43_356873M00074256D:D03 2453 37688 2458.L05.GZ43_356877 M00074258A:G05 2454 37692530.L23.beta5_566132 M00074258B:F07 2455 37702 2506.I05.GZ43_366754M00073861B:C11 2456 37707 533.K11.beta5_567155 M00074960C:H09 2457 377152467.J18.GZ43_360699 M00072983C:F04 2458 37724 533.L23.beta5_567348M00073870A:E04 2459 37729 537.A11.beta5_569833 M00073595D:H05 2460 377312535.N11.GZ43_370410 M00073596B:B12 2461 37734 2459.A22.GZ43_357014M00074274D:F10 2462 37735 537.G11.beta5_569839 M00073597A:A03 2463 377432535.O02.GZ43_370425 M00073597D:H01 2464 37748 537.D23.beta5_570028M00074293D:H07 2465 37760 537.P23.beta5_570040 M00074296B:B11 2466 37764529.D12.beta5_565564 M00074134A:E08 2467 37768 2561.K01.GZ43_376472M00074135A:F02 2468 37794 527.B12.beta5_564794 M00074089D:E03 2469 37805527.M12.beta5_564805 M00074208B:F09 2470 37826 2456.H06.GZ43_356002M00074174B:H08 2471 37827 2475.H07.GZ43_362176 M00074540C:E02 2472 37831536.H11.beta5_569072 M00074541C:E08 2473 37834 536.I11.beta5_569073M00074175A:D08 2474 37859 535.C12.beta5_568699 M00074594B:A07 2475 37861535.E12.beta5_568701 M00074594B:E10 2476 37865 2480.I08.GZ43_358703M00074596D:B12 2477 37868 535.L12.beta5_568708 M00073514A:G01 2478 378742368.H23.GZ43_346569 M00073532C:H12 2479 37877 2481.B11.GZ43_358922M00074633B:H01 2480 37882 535.J24.beta5_568898 M00073537D:C03 2481 378872481.C09.GZ43_358944 M00074635B:C07 2482 37895 2465.H15.GZ43_358247M00074890B:C01 2483 37897 2465.H17.GZ43_358249 M00074890B:D05 2484 37914532.J24.beta5_566978 M00073925B:A01 2485 37926 531.F12.beta5_566398M00074315C:F09 2486 37929 531.I12.beta5_566401 M00074713B:F02 2487 37947531.K24.beta5_566595 M00074735C:A11 2488 37951 531.O24.beta5_566599M00074735D:G06 2489 38020 2498.M13.GZ43_365152 M00075444D:F05 2490 380222498.M15.GZ43_365154 M00075448D:A02 2491 38026 530.J12.beta5_565954M00075414D:G01 2492 38029 2565.N09.GZ43_398087 M00073773D:B10 2493 38048530.P24.beta5_566152 M00075474C:G02 2494 38050 2496.A04.GZ43_364087M00075235C:E03 2495 38068 533.D24.beta5_567356 M00075283A:F04 2496 38074533.J24.beta5_567362 M00075285D:A02 2497 38083 2466.C04.GZ43_360133M00074918B:F03 2498 38089 2466.C16.GZ43_360145 M00074919C:D12 2499 380912466.C22.GZ43_360151 M00074919D:H09 2500 38096 537.P12.beta5_569864M00074754C:G02 2501 38101 537.E24.beta5_570045 M00074935A:D06 2502 38103537.G24.beta5_570047 M00074935B:C06 2503 38107 537.K24.beta5_570051M00074935C:E08 2504 38110 537.N24.beta5_570054 M00074782B:F01 2505 38112537.P24.beta5_570056 M00074783B:B11

Table 16 provides the results for gene products expressed by at least2-fold or greater in the prostate tumor samples relative to normaltissue samples in at least 20% of the patients tested. Table 16includes: 1) the spot identification number (“Spot ID”); 2) the GenBankAccession Number of the publicly available sequence corresponding to thepolynucleotide (“GenBankHit”); 3) a description of the GenBank sequence(“GenBankDesc”); 4) the score of the similarity of the polynucleotidesequence and the GenBank sequence (“GenBankScore”); 5) the number ofpatients analyzed; 6) the percentage of patients tested in whichexpression levels (e.g., as message level) of the gene was at least2-fold greater in cancerous tissue than in matched normal tissue(“>=2×”); 7) the percentage of patients tested in which expressionlevels (e.g., as message level) of the gene was at least 5-fold greaterin cancerous tissue than in matched normal tissue (“>=5×”); and 8) thepercentage of patients tested in which expression levels (e.g., asmessage level) of the gene was less than or equal to ½ of the expressionlevel in matched normal cells (“<=half×”).

Table 17 provides the results for gene products in which expressionlevels of the gene in prostate tumor cells was less than or equal to ½of the expression level in normal tissue samples in at least 20% of thepatients tested. Table 17 includes: 1) the spot identification number(“Spot ID”); 2) the GenBank Accession Number of the publicly availablesequence corresponding to the polynucleotide (“GenBankHit”); 3) adescription of the GenBank sequence (“GenBankDesc”); 4) the score of thesimilarity of the polynucleotide sequence and the GenBank sequence(“GenBankScore”); 5) the number of patients analyzed; 6) the percentageof patients tested in which expression levels (e.g., as message level)of the gene was at least 2-fold greater in cancerous tissue than inmatched normal tissue (“>=2×”); 7) the percentage of patients tested inwhich expression levels (e.g., as message level) of the gene was atleast 5-fold greater in cancerous tissue than in matched normal tissue(“>=5×”); and 8) the percentage of patients tested in which expressionlevels (e.g., as message level) of the gene was less than or equal to ½of the expression level in matched normal cells (“<=half×”).

Tables 16 and 17 also include the results from each patient, identifiedby the patient ID number (e.g., 93). This data represents the ratio ofdifferential expression for the samples tested from that particularpatient's tissues (e.g., “93” is the ratio from the tissue samples ofpatient ID no. 93). The ratios of differential expression are expressedas a normalized hybridization signal associated with the tumor probedivided by the normalized hybridization signal with the normal probe.Thus, a ratio greater than 1 indicates that the gene product isincreased in expression in cancerous cells relative to normal cells,while a ratio of less than 1 indicates the opposite.

These data provide evidence that the genes represented by thepolynucleotides having the indicated sequences are differentiallyexpressed in prostate cancer as compared to normal non-cancerousprostate tissue.

Example 21 Antisense Regulation of Gene Expression

The expression of the differentially expressed genes represented by thepolynucleotides in the cancerous cells can be analyzed using antisenseknockout technology to confirm the role and function of the gene productin tumorigenesis, e.g., in promoting a metastatic phenotype.

A number of different oligonucleotides complementary to the mRNAgenerated by the differentially expressed genes identified herein can bedesigned as potential antisense oligonucleotides, and tested for theirability to suppress expression of the genes. Sets of antisense oligomersspecific to each candidate target are designed using the sequences ofthe polynucleotides corresponding to a differentially expressed gene andthe software program HYBsimulator Version 4 (available for Windows95/Windows NT or for Power Macintosh, RNAture, Inc. 1003 Health SciencesRoad, West, Irvine, Calif. 92612 USA). Factors that are considered whendesigning antisense oligonucleotides include: 1) the secondary structureof oligonucleotides; 2) the secondary structure of the target gene; 3)the specificity with no or minimum cross-hybridization to otherexpressed genes; 4) stability; 5) length and 6) terminal GC content. Theantisense oligonucleotide is designed so that it will hybridize to itstarget sequence under conditions of high stringency at physiologicaltemperatures (e.g., an optimal temperature for the cells in culture toprovide for hybridization in the cell, e.g., about 37° C.), but withminimal formation of homodimers.

Using the sets of oligomers and the HYB simulator program, three to tenantisense oligonucleotides and their reverse controls are designed andsynthesized for each candidate mRNA transcript, which transcript isobtained from the gene corresponding to the target polynucleotidesequence of interest. Once synthesized and quantitated, the oligomersare screened for efficiency of a transcript knock-out in a panel ofcancer cell lines. The efficiency of the knock-out is determined byanalyzing mRNA levels using lightcycler quantification. The oligomersthat resulted in the highest level of transcript knock-out, wherein thelevel was at least about 50%, preferably about 80-90%, up to 95% or moreup to undetectable message, are selected for use in a cell-basedproliferation assay, an anchorage independent growth assay, and anapoptosis assay.

The ability of each designed antisense oligonucleotide to inhibit geneexpression is tested through transfection into LNCaP, PC3, 22Rv1,MDA-PCA-2b, or DU145 prostate carcinoma cells. For each transfectionmixture, a carrier molecule (such as a lipid, lipid derivative,lipid-like molecule, cholesterol, cholesterol derivative, orcholesterol-like molecule) is prepared to a working concentration of 0.5mM in water, sonicated to yield a uniform solution, and filtered througha 0.45 μm PVDF membrane. The antisense or control oligonucleotide isthen prepared to a working concentration of 100 μM in sterile Milliporewater. The oligonucleotide is further diluted in OptiMEM™ (Gibco/BRL),in a microfuge tube, to 2 μM, or approximately 20 μg oligo/ml ofOptiMEM™. In a separate microfuge tube, the carrier molecule, typicallyin the amount of about 1.5-2 nmol carrier/μg antisense oligonucleotide,is diluted into the same volume of OptiMEM™ used to dilute theoligonucleotide. The diluted antisense oligonucleotide is immediatelyadded to the diluted carrier and mixed by pipetting up and down.Oligonucleotide is added to the cells to a final concentration of 30 nM.

The level of target mRNA that corresponds to a target gene of interestin the transfected cells is quantitated in the cancer cell lines usingthe Roche LightCycler™ real-time PCR machine. Values for the target mRNAare normalized versus an internal control (e.g., beta-actin). For each20 μl reaction, extracted RNA (generally 0.2-1 μg total) is placed intoa sterile 0.5 or 1.5 ml microcentrifuge tube, and water is added to atotal volume of 12.5 μl. To each tube is added 7.5 μl of a buffer/enzymemixture, prepared by mixing (in the order listed) 2.5 μl H₂O, 2.0 μl 10×reaction buffer, 10 μl oligo dT (20 μmol), 1.0 μl dNTP mix (10 mM each),0.5 μl RNAsin® (20 u) (Ambion, Inc., Hialeah, Fla.), and 0.5 μl MMLVreverse transcriptase (50 u) (Ambion, Inc.). The contents are mixed bypipetting up and down, and the reaction mixture is incubated at 42° C.for 1 hour. The contents of each tube are centrifuged prior toamplification.

An amplification mixture is prepared by mixing in the following order:1×PCR buffer II, 3 mM MgCl₂, 140 μM each dNTP, 0.175 μmol each oligo,1:50,000 dil of SYBR® Green, 0.25 mg/ml BSA, 1 unit Taq polymerase, andH₂O to 20 μl. (PCR buffer II is available in 10× concentration fromPerkin-Elmer, Norwalk, Conn.). In 1× concentration it contains 10 mMTris pH 8.3 and 50 mM KCl. SYBR® Green (Molecular Probes, Eugene, Oreg.)is a dye which fluoresces when bound to double stranded DNA. As doublestranded PCR product is produced during amplification, the fluorescencefrom SYBR® Green increases. To each 20 μl aliquot of amplificationmixture, 2 μl of template RT is added, and amplification is carried outaccording to standard protocols. The results are expressed as thepercent decrease in expression of the corresponding gene productrelative to non-transfected cells, vehicle-only transfected(mock-transfected) cells, or cells transfected with reverse controloligonucleotides.

Example 22 Effect of Expression on Proliferation

The effect of gene expression on the inhibition of cell proliferationcan be assessed in metastatic breast cancer cell lines (MDA-MB-231(“231”)); SW620 colon colorectal carcinoma cells; SKOV3 cells (a humanovarian carcinoma cell line); or LNCaP, PC3, 22Rv1, MDA-PCA-2b, or DU145prostate cancer cells.

Cells are plated to approximately 60-80% confluency in 96-well dishes.Antisense or reverse control oligonucleotide is diluted to 2 μM inOptiMEM™. The oligonucleotide-OptiMEM™ can then be added to a deliveryvehicle, which delivery vehicle can be selected so as to be optimizedfor the particular cell type to be used in the assay. The oligo/deliveryvehicle mixture is then further diluted into medium with serum on thecells. The final concentration of oligonucleotide for all experimentscan be about 300 nM.

Antisense oligonucleotides are prepared as described above (see Example21). Cells are transfected overnight at 37° C. and the transfectionmixture is replaced with fresh medium the next morning. Transfection iscarried out as described above in Example 21.

Those antisense oligonucleotides that result in inhibition ofproliferation of SW620 cells indicate that the corresponding gene playsa role in production or maintenance of the cancerous phenotype incancerous colon cells. Those antisense oligonucleotides that inhibitproliferation in SKOV3 cells represent genes that play a role inproduction or maintenance of the cancerous phenotype in cancerous breastcells. Those antisense oligonucleotides that result in inhibition ofproliferation of MDA-MB-231 cells indicate that the corresponding geneplays a role in production or maintenance of the cancerous phenotype incancerous ovarian cells. Those antisense oligonucleotides that inhibitproliferation in LNCaP, PC3, 22Rv1, MDA-PCA-2b, or DU145 cells representgenes that play a role in production or maintenance of the cancerousphenotype in cancerous prostate cells.

Example 23 Effect of Gene Expression on Cell Migration

The effect of gene expression on the inhibition of cell migration can beassessed in LNCaP, PC3, 22Rv1, MDA-PCA-2b, or DU145 prostate cancercells using static endothelial cell binding assays, non-staticendothelial cell binding assays, and transmigration assays.

For the static endothelial cell binding assay, antisenseoligonucleotides are prepared as described above (see Example 21). Twodays prior to use, prostate cancer cells (CaP) are plated andtransfected with antisense oligonucleotide as described above (seeExamples 21 and 22). On the day before use, the medium is replaced withfresh medium, and on the day of use, the medium is replaced with freshmedium containing 2 μM CellTracker green CMFDA (Molecular Probes, Inc.)and cells are incubated for 30 min. Following incubation, CaP medium isreplaced with fresh medium (no CMFDA) and cells are incubated for anadditional 30-60 min. CaP cells are detached using CMF PBS/2.5 mM EDTAor trypsin, spun and resuspended in DMEM/1% BSA/10 mM HEPES pH 7.0.Finally, CaP cells are counted and resuspended at a concentration of1×10⁶ cells/ml.

Endothelial cells (EC) are plated onto 96-well plates at 40-50%confluence 3 days prior to use. On the day of use, EC are washed 1× withPBS and 50λ DMDM/1% BSA/10 mM HEPES pH 7 is added to each well. To eachwell is then added 50K (50λ) CaP cells in DMEM/1% BSA/10 mM HEPES pH 7.The plates are incubated for an additional 30 min and washed 5× with PBScontaining Ca⁺⁺ and Mg⁺⁺. After the final wash, 100 μL PBS is added toeach well and fluorescence is read on a fluorescent plate reader(Ab492/Em 516 nm).

For the non-static endothelial cell binding assay, CaP are prepared asdescribed above. EC are plated onto 24-well plates at 30-40% confluence3 days prior to use. On the day of use, a subset of EC are treated withcytokine for 6 hours then washed 2× with PBS. To each well is then added150-200K CaP cells in DMEM/1% BSA/10 mM HEPES pH 7. Plates are placed ona rotating shaker (70 RPM) for 30 min and then washed 3× with PBScontaining Ca⁺⁺ and Mg⁺⁺. After the final wash, 500 μL PBS is added toeach well and fluorescence is read on a fluorescent plate reader(Ab492/Em 516 nm).

For the transmigration assay, CaP are prepared as described above withthe following changes. On the day of use, CaP medium is replaced withfresh medium containing 5 μM CellTracker green CMFDA (Molecular Probes,Inc.) and cells are incubated for 30 min. Following incubation, CaPmedium is replaced with fresh medium (no CMFDA) and cells are incubatedfor an additional 30-60 min. CaP cells are detached using CMF PBS/2.5 mMEDTA or trypsin, spun and resuspended in EGM-2-MV medium. Finally, CaPcells are counted and resuspended at a concentration of 1×10⁶ cells/ml.

EC are plated onto FluorBlok transwells (BD Biosciences) at 30-40%confluence 5-7 days before use. Medium is replaced with fresh medium 3days before use and on the day of use. To each transwell is then added50K labeled CaP. 30 min prior to the first fluorescence reading, 10 μgof FITC-dextran (10K MW) is added to the EC plated filter. Fluorescenceis then read at multiple time points on a fluorescent plate reader(Ab492/Em 516 nm).

Those antisense oligonucleotides that result in inhibition of binding ofLNCaP, PC3, 22Rv1, MDA-PCA-2b, or DU145 prostate cancer cells toendothelial cells indicate that the corresponding gene plays a role inthe production or maintenance of the cancerous phenotype in cancerousprostate cells. Those antisense oligonucleotides that result ininhibition of endothelial cell transmigration by LNCaP, PC3, 22Rv1,MDA-PCA-2b, or DU145 prostate cancer cells indicate that thecorresponding gene plays a role in the production or maintenance of thecancerous phenotype in cancerous prostate cells.

Example 24 Effect of Gene Expression on Colony Formation

The effect of gene expression upon colony formation of SW620 cells,SKOV3 cells, MD-MBA-231 cells, LNCaP cells, PC3 cells, 22Rv1 cells,MDA-PCA-2b cells, and DU145 cells can be tested in a soft agar assay.Soft agar assays are conducted by first establishing a bottom layer of 2ml of 0.6% agar in media plated fresh within a few hours of layering onthe cells. The cell layer is formed on the bottom layer by removingcells transfected as described above from plates using 0.05% trypsin andwashing twice in media. The cells are counted in a Coulter counter, andresuspended to 10⁶ per ml in media. 10 μl aliquots are placed with mediain 96-well plates (to check counting with WST1), or diluted further forthe soft agar assay. 2000 cells are plated in 800 μl 0.4% agar induplicate wells above 0.6% agar bottom layer. After the cell layer agarsolidifies, 2 ml of media is dribbled on top and antisense or reversecontrol oligo (produced as described above) is added without deliveryvehicles. Fresh media and oligos are added every 3-4 days. Colonies formin 10 days to 3 weeks. Fields of colonies are counted by eye. Wst-1metabolism values can be used to compensate for small differences instarting cell number. Larger fields can be scanned for visual record ofdifferences.

Those antisense oligonucleotides that result in inhibition of colonyformation of SW620 cells indicate that the corresponding gene plays arole in production or maintenance of the cancerous phenotype incancerous colon cells. Those antisense oligonucleotides that inhibitcolony formation in SKOV3 cells represent genes that play a role inproduction or maintenance of the cancerous phenotype in cancerous breastcells. Those antisense oligonucleotides that result in inhibition ofcolony formation of MDA-MB-231 cells indicate that the correspondinggene plays a role in production or maintenance of the cancerousphenotype in cancerous ovarian cells. Those antisense oligonucleotidesthat inhibit colony formation in LNCaP, PC3, 22Rv1, MDA-PCA-2b, or DU145cells represent genes that play a role in production or maintenance ofthe cancerous phenotype in cancerous prostate cells.

Example 25 Induction of Cell Death Upon Depletion of Polypeptides byDepletion of mRNA (“Antisense Knockout”)

In order to assess the effect of depletion of a target message upon celldeath, LNCaP, PC3, 22Rv1, MDA-PCA-2b, or DU145 cells, or other cellsderived from a cancer of interest, can be transfected for proliferationassays. For cytotoxic effect in the presence of cisplatin (cis), thesame protocol is followed but cells are left in the presence of 2 μMdrug. Each day, cytotoxicity is monitored by measuring the amount of LDHenzyme released in the medium due to membrane damage. The activity ofLDH is measured using the Cytotoxicity Detection Kit from RocheMolecular Biochemicals. The data is provided as a ratio of LDH releasedin the medium vs. the total LDH present in the well at the same timepoint and treatment (rLDH/tLDH). A positive control using antisense andreverse control oligonucleotides for BCL2 (a known anti-apoptotic gene)is included; loss of message for BCL2 leads to an increase in cell deathcompared with treatment with the control oligonucleotide (backgroundcytotoxicity due to transfection).

Example 26 Functional Analysis of Gene Products Differentially Expressedin Prostate Cancer in Patients

The gene products of sequences of a gene differentially expressed incancerous cells can be further analyzed to confirm the role and functionof the gene product in tumorigenesis, e.g., in promoting or inhibitingdevelopment of a metastatic phenotype. For example, the function of geneproducts corresponding to genes identified herein can be assessed byblocking function of the gene products in the cell. For example, wherethe gene product is secreted or associated with a cell surface membrane,blocking antibodies can be generated and added to cells to examine theeffect upon the cell phenotype in the context of, for example, thetransformation of the cell to a cancerous, particularly a metastatic,phenotype. In order to generate antibodies, a clone corresponding to aselected gene product is selected, and a sequence that represents apartial or complete coding sequence is obtained. The resulting clone isexpressed, the polypeptide produced isolated, and antibodies generated.The antibodies are then combined with cells and the effect upontumorigenesis assessed.

Where the gene product of the differentially expressed genes identifiedherein exhibits sequence homology to a protein of known function (e.g.,to a specific kinase or protease) and/or to a protein family of knownfunction (e.g., contains a domain or other consensus sequence present ina protease family or in a kinase family), then the role of the geneproduct in tumorigenesis, as well as the activity of the gene product,can be examined using small molecules that inhibit or enhance functionof the corresponding protein or protein family.

Additional functional assays include, but are not necessarily limitedto, those that analyze the effect of expression of the correspondinggene upon cell cycle and cell migration. Methods for performing suchassays are well known in the art.

Example 27 Contig Assembly and Additional Gene Characterization

The sequences of the polynucleotides provided in the present inventioncan be used to extend the sequence information of the gene to which thepolynucleotides correspond (e.g., a gene, or mRNA encoded by the gene,having a sequence of the polynucleotide described herein). This expandedsequence information can in turn be used to further characterize thecorresponding gene, which in turn provides additional information aboutthe nature of the gene product (e.g., the normal function of the geneproduct). The additional information can serve to provide additionalevidence of the gene product's use as a therapeutic target, and providefurther guidance as to the types of agents that can modulate itsactivity.

In one example, a contig is assembled using a sequence of apolynucleotide of the present invention, which is present in a clone. A“contig” is a contiguous sequence of nucleotides that is assembled fromnucleic acid sequences having overlapping (e.g., shared or substantiallysimilar) sequence information. The sequences of publicly-available ESTs(Expressed Sequence Tags) and the sequences of various clones fromseveral cDNA libraries synthesized at Chiron can be used in the contigassembly.

The contig is assembled using the software program Sequencher, version4.05, according to the manufacturer's instructions and an overviewalignment of the contiged sequences is produced. The sequenceinformation obtained in the contig assembly can then be used to obtain aconsensus sequence derived from the contig using the Sequencher program.The consensus sequence is used as a query sequence in a TeraBLASTNsearch of the DGTI DoubleTwist Gene Index (DoubleTwist, Inc., Oakland,Calif.), which contains all the EST and non-redundant sequence in publicdatabases.

Through contig assembly and the use of homology searching softwareprograms, the sequence information provided herein can be readilyextended to confirm, or confirm a predicted, gene having the sequence ofthe polynucleotides described in the present invention. Further theinformation obtained can be used to identify the function of the geneproduct of the gene corresponding to the polynucleotides describedherein. While not necessary to the practice of the invention,identification of the function of the corresponding gene, can provideguidance in the design of therapeutics that target the gene to modulateits activity and modulate the cancerous phenotype (e.g., inhibitmetastasis, proliferation, and the like).

Example 28 Expression of Chondroitin 4-O Sulfotransferase 2 (C4S-2)

Laser Capture Microdissection (LCM) was used to dissect cancerous cells,as well as peritumoral normal cells from patients with prostate cancer(various grades), colon cancer, breast cancer and stomach cancer. TotalRNA was prepared from these samples by standard methods. cDNA probeswere made from this RNA and fluorescently labeled. The labeled cDNAswere used to probe a microarray chip containing sequences of multiplegenes. As shown in Table 16, Spot ED 25837, which corresponds tochondroitin 4-O sulfotransferase 2 (C4S-2) and SEQ ID 847 (see Table15), revealed a differential expression between normal and cancerouscells. The data displayed in FIG. 22 show an up-regulation of C4S-2 mRNAin prostate, colon and stomach cancer. The table headings are asfollows: “# Patients” indicates the number of patients whose RNA wasanalyzed for each cancer type, and the percentages of each of thepatient groups is expressed in the table; “>2×” indicates a greater thantwo-fold up-regulation (cancer over normal) at the mRNA level; “>5×”indicates a greater than 5-fold up-regulation at the mRNA level; “<0.5×”indicates a greater than 2-fold down-regulation at the mRNA level.Further experimental details of this example may be found in Example 20of this disclosure.

Trending analysis revealed that several genes trend in patientexpression with C4S-2 (FIG. 34). These genes may have significance inpathways, both upstream and downstream of C4S-2.

Example 29 C4S-2 mRNA Expression in Laser Capture Microdissected Tissues

Quantitative PCR of a number of normal tissues and tumor cell lines,particularly colorectal and prostate carcinoma cell lines was used toanalyze expression of C4S2. Quantitative real-time PCR was performed byfirst isolating RNA from cells using a Roche RNA Isolation kit accordingto manufacturer's directions. One microgram of RNA was used tosynthesize a first-strand cDNA using MMLV reverse transcriptase (Ambion)using the manufacturers buffer and recommended concentrations of oligodT, nucleotides, and Rnasin.

First, primers were designed. The primers were blasted against knowngenes and sequences to confirm the specificity of the primers to thetarget. The sequences of the primers are, for set 1: Forward:ATCTCCGCCTTCCGCAGCAA (SEQ ID NO: 14067) and reverse:TCGTTGAAGGGCGCCAGCTT (SEQ ID NO: 14068), and set 2: forward:CATCTACTGCTACGTG (SEQ ID NO: 14069) and reverse: ACTTCTTGAGCTTGACC (SEQID NO: 14070). These primers were used in a test qPCR using the primersagainst normal RTd tissue, as well as a mock RT to pick up levels ofpossible genomic contamination.

Quantitative PCR of a panel of normal tissue, total cancer tissue, LCMtissue, and cancer cell lines were used to determine the expressionlevels of C4S2. qPCR was performed by first isolating the RNA from theabove mentioned tissue/cells using a Qiagen RNeasy mini prep kit. In thecase of the LCM tissue, RNA was amplified via PCR to increaseconcentration after initial RNA isolation. 0.5 micrograms of RNA wasused to generate a first strand cDNA using Stratagene MuLV ReverseTranscriptase, using recommended concentrations of buffer, enzyme, andRnasin. Concentrations and volumes of dNTP, and oligo dT, or randomhexamers were lower than recommended to reduce the level of backgroundprimer dimerization in the qPCR.

The cDNA is then used for qPCR to determine the levels of expression ofC4S2 using the GeneAmp 7000 by ABI as recommended by the manufacturer.Primers for housekeeping were also run in order to normalized thevalues, and eliminate possible variations in cDNA templateconcentrations, pipetting error, etc. Three housekeepers were rundepending on the type of tissue, beta-actin for cell lines, GusB for LCMtissue, HPRT for whole tissue.

A subset of patient RNA used to probe the microarray chip was analyzedby semi-quantitative RT-PCR to confirm the microarray results. Pools of7 or 8 patient RNA samples were analyzed using primers that specificallyrecognize C4S-2. The data is expressed as mRNA expression level relativeto a housekeeping gene (GUSB). Consistent with the microarray data, thedata, displayed in FIG. 23, show an up-regulation of C4S-2 mRNA inprostate and colon cancer and a down-regulation in breast cancer.Furthermore, the data reveal that peri-tumoral normal cells in highgrade prostate cancer display an elevated expression relative toperi-tumoral normal cells in low grade prostate cancer, suggesting aglobal up-regulation of C4S-2 mRNA with progression in grade. “(2×)”indicates RNA was amplified two times; “N” indicates peri-tumoral normalepithelial cells; “C” indicates cancerous epithelial cells; “LG”indicates low grade; “HG” indicates high grade.

Example 30 C4S-2 mRNA Expression in Tissue Samples

Using the RT-PCR methods described above, C4S-2 specific primers wereused to assess the expression of C4S-2 mRNA obtained from normal tissues(from commercial sources), as well as RNA expression whole tumor tissue(pools of 7 or 8 patients). This tissue contains cell types other thanepithelium. The data is expressed as mRNA expression level relative to ahousekeeping gene (HPRT). The data, shown in FIG. 24, reveal that C4S-2mRNA is ubiquitously expressed, throughout the body, with highestexpression in normal adrenal, lung and breast tissue. The data furtherreveal significant expression in colon and prostate cancer (marked witha “C”) and down-regulation in breast cancer, relative to normal breasttissue.

Example 31 C4S-2 mRNA Expression in Prostate Cell Lines

Using the RT-PCR methods described above, C4S-2 specific primers wereused to assess the expression of C4S-2 mRNA obtained from variousprostate cell lines. The data is expressed as mRNA expression levelrelative to a housekeeping gene (actin). The data, displayed in FIG. 25,show that C4S-2 mRNA is expressed at higher levels in cell lines derivedfrom prostate cancer tumors than in cell lines derived from normalprostate epithelium.

Example 32 Antisense Regulation of C4S-2 Expression

Additional functional information on C4S-2 was generated using antisenseknockout technology. A number of different oligonucleotidescomplementary to C4S-2 mRNA were designed (FIG. 26) as potentialantisense oligonucleotides, and tested for their ability to suppressexpression of C4S-2. For each transfection mixture, a carrier molecule,preferably a lipitoid or cholesteroid, was prepared to a workingconcentration of 0.5 mM in water, sonicated to yield a uniform solution,and filtered through a 0.45 μm PVDF membrane. The antisense or controloligonucleotide was then prepared to a working concentration of 100 μMin sterile Millipore water. The oligonucleotide was further diluted inOptiMEM™ (Gibco/BRL), in a microfuge tube, to 2 μM, or approximately 20μg oligo/ml of OptiMEM™. In a separate microfuge tube, lipitoid orcholesteroid, typically in the amount of about 1.5-2 nmol lipitoid/μgantisense oligonucleotide, was diluted into the same volume of OptiMEM™used to dilute the oligonucleotide. The diluted antisenseoligonucleotide was immediately added to the diluted lipitoid and mixedby pipetting up and down. Oligonucleotide was added to the cells to afinal concentration of 30 nM.

The level of target mRNA (C4S-2) in the transfected cells wasquantitated in the cancer cell lines using the methods described above.Values for the target mRNA were normalized versus an internal control(e.g., beta-actin). For each 20 μl reaction, extracted RNA (generally0.2-1 μg total) was placed into a sterile 0.5 or 1.5 ml microcentrifugetube, and water was added to a total volume of 12.5 μl. To each tube wasadded 7.5 μl of a buffer/enzyme mixture, prepared by mixing (in theorder listed) 2.5 μl H₂O, 2.0 μl 10× reaction buffer, 10 μl oligo dT (20μmol), 1.0 μl dNTP mix (10 mM each), 0.5 μl RNAsin® (20 u) (Ambion,Inc., Hialeah, Fla.), and 0.5 μl MMLV reverse transcriptase (50 u)(Ambion, Inc.). The contents were mixed by pipetting up and down, andthe reaction mixture was incubated at 42° C. for 1 hour. The contents ofeach tube were centrifuged prior to amplification.

An amplification mixture was prepared by mixing in the following order:1×PCR buffer II, 3 mM MgCl₂, 140 μM each dNTP, 0.175 μmol each oligo,1:50,000 dil of SYBR® Green, 0.25 mg/ml BSA, 1 unit Taq polymerase, andH₂O to 20 (PCR buffer II is available in 10× concentration fromPerkin-Elmer, Norwalk, Conn.). In 1× concentration it contains 10 mMTris pH 8.3 and 50 mM KCl. SYBR® Green (Molecular Probes, Eugene, Oreg.)is a dye which fluoresces when bound to double stranded DNA. As doublestranded PCR product is produced during amplification, the fluorescencefrom SYBR® Green increases. To each 20 μl aliquot of amplificationmixture, 2 μl of template RT was added, and amplification was carriedout according to standard protocols.

FIG. 26 shows examples of anti-sense oligonucleotide sequences thatinhibit C4S-2 mRNA expression when transfected into cells. Functionaldata described in the following examples was obtained using C210-3, 4 &6. C4S-2 mRNA reduction ranged from about 60 to about 90%, as comparedto cells transfected with reverse (i.e. sense) control oligonucleotides.

In separate experiments, inhibitory RNA molecules are used to inhibitC4S-2 mRNA expression in cells. FIG. 27 lists inhibitory RNAoligonucleotides that may be used in these experiments.

Example 33 Effects of C4S-2 Antisense Molecules on CellularProliferation

PC3 cells were plated at 5000 cells/well in 96-well plate and grownovernight. Reverse control or antisense oligonucleotide was diluted to 2μM in OptiMEM™ and mixed with 30 μM Lipitoid1, a delivery vehicle, alsodiluted in OptiMEM™. This mixture of oligonucleotide and lipitoid inOptiMEM™ was then mixed with serum containing medium and then overlayedonto the cells overnight. The next day the transfection mix was removedand replaced with fresh media. Final concentration of oligonucleotidefor these experiments was 300 nM and the ratio of oligonucleotide toLipitoid 1 was 1.5 nmol lipoid per oligonucleotide. Cell proliferationwas quantified using CyQUANT® Cell Proliferation Assay Kit (MolecularProbes #C-7026).

MDAPca2b cells were plated to 50% confluency and similarly transfectedwith 300 nM reverse control or antisense oligonucleotide with 30 μMLipitoid1 overnight. After transfection, the cells were detached withtrypsin, washed twice with medium, counted and plated at 5000 cells/wellin 96-well plates. Cell proliferation was quantified usingCellTiter-Glo™ Luminescent Cell Viability Assay (Promega #G7573).

Using these methods, anti-sense oligonucleotides described in FIG. 26were transfected into PC3 cells. This usually resulted in a 60-90%knockdown of C4S-2 mRNA compared to controls. As controls, cells wereleft either untreated or were transfected with reverse controloligonucleotides. The cells were assessed for their ability to grow ontissue culture plastic in a time course that spanned 7 days. The numberof cells on any given day was assessed using either the CyQuant assay orthe luciferase assay. As shown in the two repeats of the same experimentdescribed in FIG. 28, the ability of PC3 cells to grow in vitro isinhibited by anti-sense oligonucleotides that inhibit C4S-2 expression.

Anti-sense oligonucleotides described in FIG. 26 were transfected intoMDA Pca 2b cells. This resulted in a 60-90% knockdown of C4S-2 mRNA. Ascontrols, cells were left either untreated or were transfected withreverse control oligonucleotides. The cells were assessed for theirability to grow on tissue culture plastic in a time course that spanned7 days. The number of cells on any given day was assessed using eitherthe CyQuant assay or the luciferase assay (depending on the experiment).As shown in FIG. 29, the ability of MDA Pca 2b cells to grow in vitro isinhibited by anti-sense oligonucleotides that inhibit C4S-2 expression(“RC” is a control oligonucleotide; measurements 1, 2 and 3 were takenon three days).

Example 34 Effects of C4S-2 Antisense Molecules on Colony Formation

The effect of C4S-2 expression upon colony formation was tested in asoft agar assay. Soft agar assays were conducted by first establishing abottom layer of 2 ml of 0.6% agar in media plated fresh within a fewhours of layering on the cells. The cell layer was formed on the bottomlayer by removing cells transfected as described above from plates using0.05% trypsin and washing twice in media. The cells were counted in aCoulter counter, and resuspended to 10⁶ per ml in media. 10 μl aliquotsare placed with media in 96-well plates (to check counting with WST1),or diluted further for soft agar assay. 2000 cells are plated in 800 μl0.4% agar in duplicate wells above 0.6% agar bottom layer. After thecell layer agar solidifies, 2 ml of media is dribbled on top andantisense or reverse control oligo is added without delivery vehicles.Fresh media and oligos are added every 3-4 days. Colonies are formed in10 days to 3 weeks. Fields of colonies were counted by eye.

PC3 cells were transfected as described above. Transfected cells werethen assessed for their ability to grow in soft-agar to determine theeffect of inhibiting C4S-2 on anchorage-independent growth. PC3 cellswere plated at either 400, 600 or 1000 (“1 k”) cells per well. Multipletransfection conditions were used (L1 or L1/C1). As shown in FIG. 30,PC3 cells transfected with C4S-2 anti-sense oligos consistently yieldedfewer colonies than those transfected with reverse control oligos. “UT”denotes untransfected cells; “RC” denotes transfected with reversecontrol oligos; “AS” denotes transfected with anti-sense oligos; MDA Pca2b cells were transfected as described above and also assessed for theirability to grow in soft-agar to determine the effect of inhibiting C4S-2on anchorage-independent growth. MDA Pca 2b cells were plated at either400, 600 or 1000 cells per well. As shown in FIG. 31, MDA Pca 2b cellstransfected with C4S-2 anti-sense oligos consistently yielded fewercolonies than those transfected with reverse control oligos.

Example 34 Effects of C4S-2 Antisense Molecules on Spheroids

Spheroids were assayed as follows: briefly, 96-well plates were coatedwith poly(2-hydroxyethyl methacrylate or poly-HEMA at 12 ug/ml in 95%ethanol. Poly-HEMA was slowly evaporated at room temperature untilplates were dry. Prior to adding cells plates were rinsed twice with1×PBS. Approximately 10 000 cells/well were then added and transfectedwith either anti-sense or reverse control oligonucleotide, directly insuspension with similar conditions as described elsewhere. The cellswere allowed to grow in suspension for 5 days. The effects of inhibitingC4S-2 mRNA expression were assessed both visually and using the LDHassay to assess degree of cytotoxicity.

Lactate dehydrogenase (LDH) activity is measured, using the CytotoxicityDetection Kit (Roche Catalog number: 1 644 793) by collecting culturesupernatant and adding 100 ul ALPHA MEM medium w/o FBS in V-bottom 96well plate, transferring all the culture supernatant (100 ul) to theV-bottom plate, mixing, spinning the plate at 2000 rpm for 10 mins, andremoving 100 μl for an LDH assay. Alternatively, culture supernatant wasremoved, and 200 μl ALPHA MEM medium w/o FBS and containing 2% Triton-X100 was added to the plate, incubated for 1 minute to all for lysis,spun at 2000 rpm for 10 min and 100 μl removed for LDH detection.

LDH was measured using a 1:45 mixture of catalyst, diaphoreses/NAD⁺mixture, lyophilizate resuspended H₂O and dye solution containing sodiumlactate, respectively. 100 ul of this mix is added to each well, and thesample incubated at room temperature for 20 mins. Plates can be reat ina microtiter plate reader with 490 nm filter.

rLDH/tLDH ratio is calculated as follows: the total amount of LDH (tLDH)is calculated by adding released LDH (rLDH, from culture supernatant) tothe intracellular LDH (iLDH, from cell lysate): tLDH=rLDH+iLDH. In orderto compare the amount of cytotoxicity between AS and RC treated samples,the ratio between rLDH and tLDH is used.

MDA Pca 2b were plated under non-adherent conditions and transfected insuspension with either anti-sense or reverse control oligonucleotides.The cells were allowed to grow in suspension for 5 days. The effects ofinhibiting C4S-2 mRNA expression were assessed both visually (FIG.32A-C) and using the LDH assay to assess degree of cytotoxicity (FIG.32D). Inhibiting C4S-2 mRNA expression inhibited the ability of MDA Pca2b to grow in suspension and furthermore, induced cytotoxicity.

Example 35 Effects of C4S-2 Antisense Molecules on Cytotoxicity

Cells were transfected, and the activity of LDH was measured using theCytotoxicity Detection Kit from Roche Molecular Biochemicals, asdescribed above. The data is provided as a ratio of LDH released in themedium vs. the total LDH present in the well at the same time point andtreatment (rLDH/tLDH). MRC9 cells were transfected with multiple pairsof C4S-2 anti-sense and reverse control oligonucleotides and allowed togrow for 3 days. The C4S-2 anti-sense oligonucleotides did not inducecytoxicity (above reverse control) in this “normal” (i.e. non-cancerous)fibroblast cell line (FIG. 33A). Controls antisense molecules, such asthose for Bcl2, induced cytotoxicity. mRNA levels were also measured(FIG. 33B), showing that C4S-2 mRNA expression is lower in these cellsthan in other cells, and that no morphological differences in theantisensed cells as compared to control cells were observed (FIG. 33C).

184B5 cells were also transfected with multiple pairs of C4S-2anti-sense and reverse control oligonucleotides and allowed to grow for3 days. The C4S-2 anti-sense oligonucleotides did not induce cytoxicity(above reverse control) in this “normal” (i.e. non-cancerous) breastepithelial cell line (FIG. 34).

Example 36 Effects of C4S-2 Antisense Molecules on Proliferation ofNormal Cells

MRC9 and 184B5 cells were transfected with multiple pairs of C4S-2anti-sense and reverse control oligonucleotides and allowed to grow for4 days. The C4S-2 anti-sense oligonucleotides did not inhibitproliferation (above reverse control) in these non-cancerous cell lines(FIG. 35).

Example 37 Screening Assays

Screening assays are performed according to Burkart & Wong Anal Biochem274:131-137 (1999), with modifications.

Using primers flanking the open reading frame, C4S-2 is cloned into ashuttle vector, from which it can be shuttled into multiple expressionvectors. Protein expression is assessed using a polyclonal antibody.Activity is assessed using standard assays, i.e. those designed to assaysulfate transfer to chondroitin, chondroitin sulfate or dermatansulfate. βAST-IV is also cloned and expressed as described in the abovereport Burkart et al, supra.

C4S-2-modulatory agents are counter-screened to ensure specificity.Included in the counterscreen are C4S-1, C4S-3 and HNK1ST (closestrelatives to C4S-2 with approximately 30-42% homology). Additionally,representatives from other classes of sulfotransferases (heparinsulfotransferase, estrogen sulfotransferase, phenol sulfotransferase,tyrosine sulfotransferase) with low homology are also screened.Additionally, representatives from classes of kinases will be used inthe counter-screen.

C4S-2 will transfer a sulfonyl group from PAPS to chondroitin sulfate,thus generating PAP. βAST-IV will regenerate PAPS, using p-nitrophenylsulfate as the sulfate donor. One of the resulting products from thelatter reaction—p-nitrophenol can be monitored colorimetrically.

Inhibitors are assessed for their ability to inhibit C4S-2, asdetermined by an inhibition of p-nitrophenol generation. Control screensinclude regeneration of PAPS from PAP by βAST-IV, in the absence ofC4S-2, to ensure that inhibitors of βAST-IV are not selected. Compoundsthat inhibit C4S-2 activity are counterscreened against relevant enzymeslisted above.

Inhibitors passing the above screens are tested in cell-based functionalassays (Proliferation, LDH, spheroid and soft-agar assays). The testedcell lines include PC3, MDA Pca 2b, DU145, Colo320, KM12C, A431, MDA435,MDA469, etc. Additionally, cell lines stably transfected to over-expressC4S-2 are assessed compared to parental and control transfected lines.

Inhibitors that show efficacy in the cell line functional assays aretested in xenograft mouse models. A subset of the lines, including PC3,DU145 and MDA435, etc. is in these animal models.

Example 38 Source of Biological Materials

The cells used for detecting differential expression of breast cancerrelated genes were those previously described for the HMT-3522 tumorreversion model, disclosed in U.S. Pat. Nos. 5,846,536 and 6,123,941,herein incorporated by reference. The model utilizes bothnon-tumorigenic (HMT-3522 S1) and tumorigenic (HMT-3522 T4-2) cellsderived by serial passaging from a single reduction mammoplasty. In twodimensional (2D) monolayers on plastic, both S1 and T4-2 cells displaysimilar morphology. But in three dimensional (3D) matrigel cultures, S1form phenotypically normal mammary tissue structures while T4-2 cellsfail to organize into these structures and instead disseminate into thematrix. This assay was designated as a tumor reversion model, in thatthe T4-2 cells can be induced to form S1-like structures in 3D bytreatment with beta-1 integrin or EGFR blocking antibodies, or bytreating with a chemical inhibitor of the EGFR signaling pathway(tyrophostin AG 1478). These treated T4-2 cells, called T4R cells, arenon-tumorigenic.

Example 39 Cell Growth and RNA Isolation

Growth of Cells 2D and 3D for Microarray Experiments: HMT3522 S1 andT4-2 cells were grown 2D and 3D and T4-2 cells reverted with anti-EGFR,anti-beta 1 integrin, or tyrophostin AG 1478 as previously described(Weaver et al J. Cell Biol. 137:231-45, 1997; and Wang et al PNAS95:14821-14826, 1998). Anti-EGFR (mAb 225) was purchased from Oncogeneand introduced into the matrigel at the time of gelation at aconcentration of 4 ug/ml purified mouse IgG1. Anti-beta 1 integrin (mAbAIIB2) was a gift from C. Damsky at the University of California at SanFrancisco and was also introduced into the matrigel at the time ofgelation at a concentration of 100 ug/ml ascites protein (whichcorresponds to 4-10 ug/ml purified rat IgG1). Tyrophostin AG 1478 waspurchased from Calbiochem and used at a concentration of 100 nM.

Isolation of RNA for Microarray Experiments: RNA was prepared from: S1passage 60 2D cultures; T4-2 passage 41 2D cultures; S1 passage 59 3Dcultures; and T4-2 and T4-2 revertant (with anti-EGFR, anti-beta 1integrin, and tyrophostin) passage 35 3D cultures.

All RNA for microarray experiments was isolated using the commerciallyavailable RNeasy Mini Kit from Qiagen. Isolation of total RNA from cellsgrown 2D was performed as instructed in the kit handbook. Briefly, mediawas aspirated from the cells and kit Buffer RLT was added directly tothe flask. The cell lysate was collected with a rubber cell scraper, andthe lysate passed 5 times through a 20-G needle fitted to a syringe. Onevolume of 70% ethanol was added to the homogenized lysate and mixed wellby pipetting. Up to 700 ul of sample was applied to an RNeasy mini spincolumn sitting in a 2-ml collection tube and centrifuged for 15 secondsat >8000×g. 700 ul Buffer RW1 was added to the column and centrifugedfor 15 seconds at >8000×g to wash. The column was transferred to a newcollection tube. 500 ul Buffer RPE was added to the column andcentrifuged for 15 seconds at >8000×g to wash. Another 500 ul Buffer RPEwas added to the column for additional washing, and the columncentrifuged for 2 minutes at maximum speed to dry. The column wastransferred to a new collection tube and RNA eluted from the column with30 ul RNase-free water by centrifuging for 1 minute at >8000×g.

Isolation of total RNA from cells grown 3D was performed as describedabove, except cells were isolated from matrigel prior to RNA isolation.The cells were isolated as colonies from matrigel using ice-coldPBS/EDTA (0.01 M sodium phosphate pH 7.2 containing 138 mM sodiumchloride and 5 mM EDTA). See Weaver et al, J Cell Biol 137:231-245,1997; and Wang et al. PNAS 95:14821-14826, 1998.

Example 40 Detection and Identification of Genes Exhibiting DifferentialExpression

The relative expression levels of a selected sequence (which in turn isrepresentative of a single transcript) were examined in the tumorigenicversus non-tumorigenic cell lines described above, following culturingof the cells (S1, T4-2 and T4R) in either two-dimensional (2D)monolayers or three-dimensional (3D) matrigel cultures as describedabove. Differential expression for a selected sequence was assessed byhybridizing mRNA from S1 and T4-2 2D cultures, and S1, T4-2 and T4R 3Dcultures to microarray chips as described below, as follows: Exp1=T4-22D/S1 2D; Exp2=T4-2 3D/S1 3D; Exp3=S1 3D/S1 2D; Exp4=T4-2 3D/T4-2 2D;Exp5=T4-2 3D/T4R (anti-EGFR) 3D; Exp6=T4-2 3D/T4R (anti-beta1 integrin)3D; and Exp7=T4-2 3D/T4R (tyrophostin AG 1478) 3D.

Each array used had an identical spatial layout and control spot set.Each microarray was divided into two areas, each area having an arraywith, on each half, twelve groupings of 32×12 spots for a total of about9,216 spots on each array. The two areas are spotted identically whichprovide for at least two duplicates of each clone per array. Spottingwas accomplished using PCR amplified products from 0.5 kb to 2.0 kb andspotted using a Molecular Dynamics Gen III spotter according to themanufacturer's recommendations. The first row of each of the 24 regionson the array had about 32 control spots, including 4 negative controlspots and 8 test polynucleotides.

The test polynucleotides were spiked into each sample before thelabeling reaction with a range of concentrations from 2-600 pg/slide andratios of 1:1. For each array design, two slides were hybridized withthe test samples reverse-labeled in the labeling reaction. This providedfor about 4 duplicate measurements for each clone, two of one color andtwo of the other, for each sample.

Identification Of Differentially Expressed Genes: “Differentiallyexpressed” in the context of the present example meant that there was adifference in expression of a particular gene between tumorigenic vs.non-tumorigenic cells, or cells grown in three-dimensional culture vs.cells grown in two-dimensional culture. To identify differentiallyexpressed genes, total RNA was first reverse transcribed into cDNA usinga primer containing a T7 RNA polymerase promoter, followed by secondstrand DNA synthesis. cDNA was then transcribed in vitro to produceantisense RNA using the T7 promoter-mediated expression (see, e.g., Luoet al. (1999) Nature Med 5:117-122), and the antisense RNA was thenconverted into cDNA. The second set of cDNAs were again transcribed invitro, using the T7 promoter, to provide antisense RNA. Optionally, theRNA was again converted into cDNA, allowing for up to a third round ofT7-mediated amplification to produce more antisense RNA. Thus theprocedure provided for two or three rounds of in vitro transcription toproduce the final RNA used for fluorescent labeling.

Fluorescent probes were generated by first adding control RNA to theantisense RNA mix, and producing fluorescently labeled cDNA from the RNAstarting material. Fluorescently labeled cDNAs prepared from tumorigenicRNA sample were compared to fluorescently labeled cDNAs prepared fromnon-tumorigenic cell RNA sample. For example, the cDNA probes from thenon-tumorigenic cells were labeled with Cy3 fluorescent dye (green) andthe cDNA probes prepared from the tumorigenic cells were labeled withCy5 fluorescent dye (red).

The differential expression assay was performed by mixing equal amountsof probes from tumorigenic cells and non-tumorigenic cells, and/or cellsgrown in 3D vs. those grown in 2D. The arrays were prehybridized byincubation for about 2 hrs at 60° C. in 5×SSC/0.2% SDS/1 mM EDTA, andthen washed three times in water and twice in isopropanol. Followingprehybridization of the array, the probe mixture was then hybridized tothe array under conditions of high stringency (overnight at 42° C. in50% formamide, 5×SSC, and 0.2% SDS). After hybridization, the array waswashed at 55° C. three times as follows: 1) first wash in 1×SSC/0.2%SDS; 2) second wash in 0.1×SSC/0.2% SDS; and 3) third wash in 0.1×SSC.

The arrays were then scanned for green and red fluorescence using aMolecular Dynamics Generation III dual color laser-scanner/detector. Theimages were processed using BioDiscovery Autogene software, and the datafrom each scan set normalized to provide for a ratio of expressionrelative to non-tumorigenic or tumorigenic cells grown two-dimensionallyor three-dimensionally. Data from the microarray experiments wasanalyzed according to the algorithms described in U.S. application Ser.No. 60/252,358, filed Nov. 20, 2000, by E. J. Moler, M. A. Boyle, and F.M. Randazzo, and entitled “Precision and accuracy in cDNA microarraydata,” which application is specifically incorporated herein byreference.

The experiment was repeated, this time labeling the two probes with theopposite color in order to perform the assay in both “color directions.”Each experiment was sometimes repeated with two more slides (one in eachcolor direction). The level fluorescence for each sequence on the arrayexpressed as a ratio of the geometric mean of 8 replicate spots/genesfrom the four arrays or 4 replicate spots/gene from 2 arrays or someother permutation. The data were normalized using the spiked positivecontrols present in each duplicated area, and the precision of thisnormalization was included in the final determination of thesignificance of each differential. The fluorescence intensity of eachspot was also compared to the negative controls in each duplicated areato determine which spots have detected significant expression levels ineach sample.

A statistical analysis of the fluorescent intensities was applied toeach set of duplicate spots to assess the precision and significance ofeach differential measurement, resulting in a p-value testing the nullhypothesis that there is no differential in the expression level betweenthe tumorigenic and non-tumorigenic cells or cells growntwo-dimensionally versus three-dimensionally. During initial analysis ofthe microarrays, the hypothesis was accepted if p>10⁻³, and thedifferential ratio was set to 1.000 for those spots. All other spotshave a significant difference in expression between the two samplescompared. For example, if the tumorigenic sample has detectableexpression and the non-tumorigenic does not, the ratio is truncated at1000 since the value for expression in the non-tumorigenic sample wouldbe zero, and the ratio would not be a mathematically useful value (e.g.,infinity). If the non-tumorigenic sample has detectable expression andthe tumorigenic does not, the ratio is truncated to 0.001, since thevalue for expression in the tumor sample would be zero and the ratiowould not be a mathematically useful value. These latter two situationsare referred to herein as “on/off.” Database tables were populated usinga 95% confidence level (p>0.05).

In general, a polynucleotide is said to represent a significantlydifferentially expressed gene between two samples when there isdetectable levels of expression in at least one sample and the ratiovalue is greater than at least about 1.2 fold, at least about 1.5 fold,or at least about 2 fold, where the ratio value is calculated using themethod described above.

A differential expression ratio of 1 indicates that the expression levelof the gene in tumorigenic cells was not statistically different fromexpression of that gene in the specific non-tumorigenic cells compared.A differential expression ratio significantly greater than 1 intumorigenic breast cells relative to non-tumorigenic breast cellsindicates that the gene is increased in expression in tumorigenic cellsrelative to non-tumorigenic cells, suggesting that the gene plays a rolein the development of the tumorigenic phenotype, and may be involved inpromoting metastasis of the cell. Detection of gene products from suchgenes can provide an indicator that the cell is cancerous, and mayprovide a therapeutic and/or diagnostic target. Likewise, a differentialexpression ratio significantly less than 1 in tumorigenic breast cellsrelative to non-tumorigenic breast cells indicates that, for example,the gene is involved in suppression of the tumorigenic phenotype.Increasing activity of the gene product encoded by such a gene, orreplacing such activity, can provide the basis for chemotherapy. Suchgene can also serve as markers of cancerous cells, e.g., the absence ordecreased presence of the gene product in a breast cell relative to anon-tumorigenic breast cell indicates that the cell is cancerous.

Using the above methodology, three hundred and sixty-seven (367) genesor products thereof were identified from 20,000 chip clones analyzed asbeing overexpressed 2-fold or more in one or more of these experiments,with a p-value of 0.001 or less. These identified genes or productsthereof are listed in Table 18, according to the Spot ID of the spottedpolynucleotide, the Sample ID, the corresponding GenBank AccessionNumber (No.), the GenBank description (if available) for thecorresponding Genbank Accession Number, and the GenBank score (p-value;the probability that the association between the SEQ ID NO. and the geneor product thereof occurred by chance). The polynucleotide andpolypeptide sequences, as provided by any disclosed Genbank entries areherein incorporated by reference to the corresponding Genbank accessionnumber. The differential hybridization results from the sevendifferential expression microarray experiments listed above are providedin Table 19, where sequences have a measurement corresponding to itsratio of expression in the 7 experiments, e.g. spot ID 10594 is 2.2-foldoverexpressed in 3D T4-2 cells as compared to 3D S1 cells. SEQ IDNOS:1-3004, representing the sequences corresponding to the spot Idslisted in Tables 18 and 19 are provided in the sequence listing. Table20 is a lookup table showing the relationship between the spot Ids (i.e.the nucleic acids spotted on the microarray) and the sequences providedin the sequence listing.

TABLE 18 GENBANK GENBANK SPOTID SAMPLE ID NO GENBANK DESCRIPTION SCORE10594 I:1871362:05B01:A04 M62994 Homo sapiens thyroid autoantigen8.6E−36 (truncated actin-binding protein) mRNA, complete cds 21851M00055153A:A12 20990 I:1986550:13B02:G12 XM_005667 Homo sapienslipocalin 2 0 (oncogene 24p3) (LCN2), mRNA 18641 I:3473302:09A01:A09AB046098 Macaca fascicularis brain cDNA, 5.8E−57 clone: QccE-15843 17229I:1506962:09A01:G01 AL365454 Homo sapiens mRNA full length 2.6E−110insert cDNA clone EUROIMAGE 926491 25930 035JN020.F01 AJ010446 Homosapiens mRNA for 0 immunoglobulin kappa light chain, anti-RhD, therad 2420701 RG:730349:10010:G12 U28387 Human hexokinase II pseudogene, 0complete cds 20346 RG:1839794:10015:E11 U28387 Human hexokinase IIpseudogene, 0 complete cds 21247 M00054680C:A06 U28387 Human hexokinaseII pseudogene, 9.9E−80 complete cds 23062 M00056353C:E10 XM_011013 Homosapiens filamin B, beta 0 (actin-binding protein-278) (FLNB), mRNA 25666035Jn031.B01 AF191633 Homo sapiens filamin (FLNB) 0 gene, exon 48 andcomplete cds 19001 I:2171401:09A02:E09 AF123887 Homo sapiens ERO1L(ERO1L) 3.3E−104 mRNA, partial cds 10897 I:1852047:02A01:A10 U22384Human lysyl oxidase gene, partial 0 cds 1960 M00023297B:A10 M33376 Humanpseudo-chlordecone 0 reductase mRNA, complete cds 26381 035JN029.H02AB037838 Homo sapiens mRNA for 0 KIAA1417 protein, partial cds 26719035JN030.A02 X68277 H. sapiens CL 100 mRNA for 0 protein tyrosinephosphatase 27152 037XN007.A09 XM_048479 Homo sapiens hypotheticalprotein 7.3E−58 FLJ14642 (FLJ14642), mRNA 10926 I:2047770:08B02:G04AK000969 Homo sapiens cDNA FLJ10107 fis, 3.8E−94 clone HEMBA100258328980 035JN003.C12 XM_027456 Homo sapiens hypothetical gene 0 supportedby AK000584 (LOC89942), mRNA 1236 M00022024A:F02 29350 035JN008.D06XM_043864 Homo sapiens phosphoinositide-3- 0 kinase, regulatory subunit,polypeptide 1 (p85 alpha) (PIK3R1), mRNA 26242 035JN015.B02 AL137717Homo sapiens mRNA; cDNA 2.6E−70 DKFZp434J1630 (from clone DKFZp434J1630)4098 M00001439D:C09 BC002446 Homo sapiens, MRJ gene for a 0 member ofthe DNAJ protein family, clone MGC: 1152 IMAGE: 3346070, mRNA, completecds 17432 I:1965049:16B02:D07 XM_051165 Homo sapiens DKFZP586A0522 0protein (DKFZP586A0522), mRNA 1785 SL198 XM_051165 Homo sapiensDKFZP586A0522 0 protein (DKFZP586A0522), mRNA 28856 035JN032.E11 X62996H. sapiens mitochondrial genome 0 (consensus sequence) 18791RG:229957:10007:D03 D42042 Human mRNA for KIAA0085 gene, 0 partial cds22950 M00056922C:C09 1882 M00022196B:D09 Z29083 H. sapiens 5T4 gene for5T4 0 Oncofetal antigen 23886 M00055408A:F10 24995 M00055215C:E11XM_012880 Homo sapiens hypothetical protein 0 MGC1936 (MGC1936), mRNA24477 M00055510B:F08 AF240697 Homo sapiens retinol 0 dehydrogenasehomolog isoform-2 (RDH) mRNA, complete cds 21681 M00056771C:A12 X02152Human mRNA for lactate 0 dehydrogenase-A (LDH-A, EC 1.1.1.27) 9557I:1335140:05A02:C08 X02152 Human mRNA for lactate 0 dehydrogenase-A(LDH-A, EC 1.1.1.27) 22033 M00056574B:A07 873 M00007979C:C05 X00663Human mRNA fragment for 0 epidermal growth factor (EGF) receptor 17144RG:25254:10004:D07 M97675 Human transmembrane receptor 0 (ror1) mRNA,complete cds 26970 035JN015.F09 AF097514 Homo sapiens stearoyl-CoA 0desaturase (SCD) mRNA, complete cds 21402 M00054507C:D07 27074035Jn031.B03 AF061741 Homo sapiens retinal short-chain 0dehydrogenase/reductase retSDR1 mRNA, complete cds 10963I:1258790:05A02:B10 AF072752 Homo sapiens ten integrin EGF- 0 likerepeat domains protein precursor (ITGBL1) mRNA, complete cds 29525035JN026.D12 25514 035JN011.F01 U62961 Human succinyl CoA: 3-oxoacid 0CoA transferase precursor (OXCT) mRNA, complete cds 26612 035JN016.C08NM_000240 Homo sapiens monoamine oxidase 0 A (MAOA), nuclear geneencoding mitochondrial protein, mRNA 24600 M00055490C:G11 U57059 Homosapiens Apo-2 ligand 0 mRNA, complete cds 9741 I:3126828:12A02:G02U37518 Human TNF-related apoptosis 0 inducing ligand TRAIL mRNA,complete cds 23689 M00054752A:E11 XM_001468 Homo sapiens S100 calcium- 0binding protein A10 (annexin II ligand, calpactin I, light polypeptide(p11)) (S100A10), mRNA 22352 M00042842B:E02 XM_001468 Homo sapiens S100calcium- 0 binding protein A10 (annexin II ligand, calpactin I, lightpolypeptide (p11)) (S100A10), mRNA 23806 RG:2007319:20003:G10 12285I:1404669:04A01:G12 BC002517 Homo sapiens, Pirin, clone 0 MGC: 2083IMAGE: 3140037, mRNA, complete cds 27638 035JN011.D10 AK002155 Homosapiens cDNA FLJ11293 fis, 0 clone PLACE1009670, highly similar to Homosapiens genethonin 1 mRNA 9663 I:2488567:11A02:H08 XM_006027 Homosapiens brain-derived 0 neurotrophic factor (BDNF), mRNA 26850035JN003.B03 XM_031551 Homo sapiens similar to 0 carbohydrate (N-acetylglucosamine-6-O) sulfotransferase 2 (H. sapiens) (LOC90414), mRNA10204 I:1491445:02B01:F09 AF131765 Homo sapiens clone 24833 0nonsyndromic hearing impairment protein mRNA sequence, complete cds 13182192-6 25922 035JN020.B01 AB020673 Homo sapiens mRNA for 0 KIAA0866protein, complete cds 26347 035JN025.G02 20361 I:395116:17A02:E05 28672035JN012.A05 AF126181 Homo sapiens breast cancer- 0 associated gene 1protein (BCG1) mRNA, complete cds 25520 035JN011.A07 D86956 Human mRNAfor KIAA0201 gene, 0 complete cds 1723 M00005694A:A09 BC001980 Homosapiens, clone 0 IMAGE: 3462291, mRNA 28863 037XN002.A05 25526035JN011.D07 AF086281 Homo sapiens full length insert 0 cDNA cloneZD45G11 27936 035JN008.A04 X59445 H. sapiens mRNA for colon 0 carcinomaManganese Superoxide Dismutase 26851 035JN001.C03 XM_033944 Homo sapienssuperoxide 0 dismutase 2, mitochondrial (SOD2), mRNA 25107M00054825A:E04 AF075061 Homo sapiens full length insert 0 cDNA YP07G1024912 M00054505D:D06 AF075061 Homo sapiens full length insert 0 cDNAYP07G10 25169 M00055510D:D04 M11167 Human 28S ribosomal RNA gene 1.2E−7625600 035JN023.A01 BC003107 Homo sapiens, inhibitor of DNA 0 binding 3,dominant negative helix- loop-helix protein, clone MGC: 1988 IMAGE:3543936, mRNA, complete 28706 035JN016.B05 X55181 Human ETS2 gene, 3′end0 26377 035JN029.F02 Y14436 Homo sapiens mRNA for 0 phosphatidic acidphosphatase type 2 19460 I:438655:14B02:B04 AF007133 Homo sapiens clone23764 mRNA 4.5E−113 sequence 25243 RG:1667183:10014: BC000013 Homosapiens, insulin-like growth 0 F12 factor binding protein 3, clone MGC:2305 IMAGE: 3506666, mRNA, complete cds 20018 I:1213574:17B01:A11AB037925 Homo sapiens MAIL mRNA, 3.7E−106 complete cds 918M00026895D:H03 BC006433 Homo sapiens, Ras-related GTP- 0 bindingprotein, clone MGC: 13077 IMAGE: 3835186, mRNA, complete cds 25027RG:1983823:20002:B06 29089 035JN017.B06 XM_037534 Homo sapiensphosphodiesterase 0 7A (PDE7A), mRNA 9141 I:1347384:02A02:C07 U78579Human type I phosphatidylinositol- 0 4-phosphate 5-kinase beta (STM7)mRNA, partial cds 12005 I:1259230:05A01:C06 D87075 Human mRNA forKIAA0238 gene, 0 partial cds 12148 I:3360476:03B01:B12 XM_040922 Homosapiens interleukin 13 0 receptor, alpha 2 (IL13RA2), mRNA 17394RG:1943755:10016:A07 AF346607 Homo sapiens interleukin-1 0 receptorassociated kinase 1b (IRAK) mRNA, complete cds, alternatively spliced27017 035JN021.F03 XM_051742 Homo sapiens spermine synthase 0 (SMS),mRNA 25809 035JN002.B07 XM_009699 Homo sapiens nuclear receptor 0interacting protein 1 (NRIP1), mRNA 8719 I:2600080:10A01:H01 XM_009665Homo sapiens Kreisler (mouse) 0 maf-related leucine zipper homolog(KRML), mRNA 21030 RG:1714832:10015:C06 XM_029957 Homo sapiens Rabacceptor 1 0 (prenylated) (RABAC1), mRNA 11436 I:1470085:03B01:F05XM_038976 Homo sapiens N-ethylmaleimide- 0 sensitive factor attachmentprotein, alpha (NAPA), mRNA 10374 I:1513989:03B02:C03 XM_009010 Homosapiens complement 1.4E−96 component 3 (C3), mRNA 19037I:417827:15A01:G10 X79538 H. sapiens nuk_34 mRNA for 1.9E−28 translationinitiation factor 398 M00027016A:C05 XM_031470 Homo sapiens aldolase C,  4E−62 fructose-bisphosphate (ALDOC), mRNA 18773 I:1211682:14A02:C09XM_008477 Homo sapiens aldolase C, 0 fructose-bisphosphate (ALDOC), mRNA3583 M00023407B:C10 3418 M00001470A:C03 XM_043951 Homo sapiensCDP-diacylglycerol- 0 inositol 3-phosphatidyltransferase(phosphatidylinositol syntase) (CDIPT), mRNA 18985 I:1402615:09A02:E03AF191148 Homo sapiens type I 7.9E−64 transmembrane protein Fn14 mRNA,complete cds 25861 035JN010.D01 XM_047975 Homo sapiens hydroxyacyl 0glutathione hydrolase (HAGH), mRNA 3317 M00003974D:E04 AF136185 Homosapiens collagen type XVII 0 (COL17A1) gene; 3′ UTR, long form 8743I:1858905:04A01:D01 U36775 Human ribonuclease 4 gene, 2.1E−57 partialcds 26240 035JN015.A02 XM_007493 Homo sapiens ribonuclease, 0 RNase Afamily, 4 (RNASE4), mRNA 28562 037XN007.B11 X00947 Human alpha1-antichymotrypsin 0 gene fragment 16877 I:2362945:15A01:C07 XM_029378Homo sapiens checkpoint 1.9E−91 suppressor 1 (CHES1), mRNA 25955035JN022.C01 AF035620 Homo sapiens BRCA1-associated 0 protein 2 (BRAP2)mRNA, complete cds 26308 035JN023.C02 XM_041470 Homo sapiens zinc fingerprotein 0 145 (Kruppel-like, expressed in promyelocytic leukemia)(ZNF145), mRNA 4140 2239-4 X03083 Human lactate dehydrogenase-A 0 geneexon 7 and 3′ flanking region 3436 2239-1 X03083 Human lactatedehydrogenase-A 0 gene exon 7 and 3′ flanking region 25612 035JN023.G01M94856 Human fatty acid binding protein 0 homologue (PA-FABP) mRNA,complete cds 12257 I:1448135:04A01:A06 X15535 H. sapiens lysosomal acid0 phosphatase gene (EC 3.1.3.2) Exon 11 9111 I:1958902:04A02:D07 D87258Homo sapiens mRNA for serin 0 protease with IGF-binding motif, completecds 17620 I:875567:15B01:B08 XM_045326 Homo sapiens MAX-interacting 0protein 1 (MXI1), mRNA 26025 035JN030.F01 XM_032511 Homo sapiensprocollagen-proline, 0 2-oxoglutarate 4-dioxygenase (proline4-hydroxylase), alpha polypeptide I (P4HA1), mRNA 19271RG:686684:10010:D04 AF005216 Homo sapiens receptor-associated 0 tyrosinekinase (JAK2) mRNA, complete cds 4151 2035-1 D87953 Human mRNA for RTP,complete 0 cds 26569 035JN010.F02 AB004788 Homo sapiens mRNA for BNIP3L,0 complete cds 10344 I:2859338:11B02:D03 XM_005052 Homo sapiensangiopoietin 1 1.3E−97 (ANGPT1), mRNA 832 M00021649B:D05 XM_004628 Homosapiens hypoxia-inducible 0 protein 2 (HIG2), mRNA 12071I:1798283:06A01:D06 S72481 pantophysin [human, keratinocyte 0 lineHaCaT, mRNA, 2106 nt] 12271 I:1445767:04A01:H06 X12701 H. sapiens mRNAfor endothelial 1.8E−130 plasminogen activator inhibitor PAI 11433I:1526282:03A01:E05 XM_033627 Homo sapiens glycoprotein 3.7E−117(transmembrane) nmb (GPNMB), mRNA 20917 RG:222350:10007:C12 X00663 HumanmRNA fragment for 1.7E−122 epidermal growth factor (EGF) receptor 25810035JN004.B07 X00588 Human mRNA for precursor of 0 epidermal growthfactor receptor 12039 I:3506985:07A01:D06 M24795 Human CD36 antigenmRNA, 0 complete cds 25499 035JN005.G07 XM_028224 Homo sapiens N- 0acetylglucosamine-phosphate mutase (AGM1), mRNA 25557 035JN013.D07BC010135 Homo sapiens, cyclin C, clone 0 IMAGE: 4106819, mRNA 9917I:1283532:05A01:G09 XM_004148 Homo sapiens 5T4 oncofetal 2.4E−70trophoblast glycoprotein (5T4), mRNA 19505 RG:204653:10007:A10 XM_003789Homo sapiens colony stimulating 0 factor 1 receptor, formerly McDonoughfeline sarcoma viral (v- fms) oncogene homolog (CSF1R), mRNA 17491RG:277866:10008:B07 XM_003789 Homo sapiens colony stimulating 0 factor 1receptor, formerly McDonough feline sarcoma viral (v- fms) oncogenehomolog (CSF1R), mRNA 10683 I:1686726:06A01:F10 XM_003789 Homo sapienscolony stimulating 0 factor 1 receptor, formerly McDonough felinesarcoma viral (v- fms) oncogene homolog (CSF1R), mRNA 1936M00008020C:H09 X68277 H. sapiens CL 100 mRNA for 0 protein tyrosinephosphatase 828 M00021638B:F03 X68277 H. sapiens CL 100 mRNA for 0protein tyrosine phosphatase 9558 I:1824443:05B02:C08 XM_003708 Homosapiens gamma- 0 aminobutyric acid (GABA) A receptor, pi (GABRP), mRNA20164 I:1997963:14B02:B05 XM_003631 Homo sapiens solute carrier family 025 (mitochondrial carrier; adenine nucleotide translocator), member 4(SLC25A4), mRNA 969 NIH50_40026 BC008664 Homo sapiens, clone MGC: 9281 0IMAGE: 3871960, mRNA, complete cds 9910 I:1805840:05B01:C09 XM_003399Homo sapiens mannosidase, beta 0 A, lysosomal (MANBA), mRNA 2427M00005767D:B03 XM_047441 Homo sapiens RAP1, GTP-GDP 0 dissociationstimulator 1 (RAP1GDS1), mRNA 19990 RG:1056692:10012:C11 XM_003450 Homosapiens cyclin G associated 0 kinase (GAK), mRNA 20605I:690313:16A01:G12 XM_011152 Homo sapiens insulin-like growth 0 factorbinding protein 7 (IGFBP7), mRNA 10650 I:2456393:07B01:E10 AK001580 Homosapiens cDNA FLJ10718 fis, 0 clone NT2RP3001096, weakly similar toRattus norvegicus leprecan mRNA 25963 035JN022.G01 X53002 Human mRNA forintegrin beta-5 0 subunit 25562 035JN015.F07 X53002 Human mRNA forintegrin beta-5 0 subunit 9377 I:2782593:12A01:A02 X60656 H. sapiensmRNA for elongation 1.4E−46 factor 1-beta 17618 I:707667:15B01:A08XM_002273 Homo sapiens inhibitor of DNA 3.5E−117 binding 2, dominantnegative helix- loop-helix protein (ID2), mRNA 12136 I:3208994:03B01:D06U16267 Human AMP deaminase isoform L, 0 alternatively spliced (AMPD2)mRNA, exons 1A, 2 and 3, partial cds 17373 I:1538189:14A02:G07 XM_046818Homo sapiens similar to receptor 8.3E−123 tyrosine kinase-like orphanreceptor 1 (H. sapiens) (LOC92711), mRNA 18577 RG:503209:10010:A09XM_049305 Homo sapiens Lysosomal- 0 associated multispanning membraneprotein-5 (LAPTM5), mRNA 3143 M00001605D:C02 BC003107 Homo sapiens,inhibitor of DNA 1.7E−88 binding 3, dominant negative helix- loop-helixprotein, clone MGC: 1988 IMAGE: 3543936, mRNA, complete 17737RG:155066:10006:E02 AL050147 Homo sapiens mRNA; cDNA 0 DKFZp586E0820(from clone DKFZp586E0820); partial cds 20029 I:1923613:17A01:G11AF113123 Homo sapiens carbonyl reductase 0 mRNA, complete cds 18537NIH50_40304 BC001380 Homo sapiens, succinate 0 dehydrogenase complex,subunit A, flavoprotein (Fp), clone MGC: 1484 IMAGE: 3051442, mRNA,complete cds 10090 NIH50_40304 12102 I:2832414:11B01:C06 XM_048045 Homosapiens katanin p80 (WD40- 0 containing) subunit B1 (KATNB1), mRNA 8487I:1375115:05A01:D01 BC001174 Homo sapiens, exostoses 0 (multiple) 1,clone MGC: 2129 IMAGE: 3502232, mRNA, complete cds 9252I:1673876:06B01:B02 BC000917 Homo sapiens, clone MGC: 5184 0 IMAGE:3048750, mRNA, complete cds 25605 035JN021.D01 BC000671 Homo sapiens,claudin 4, clone 0 MGC: 1778 IMAGE: 3349211, mRNA, complete cds 29652M00001610C:D05 BC000588 Homo sapiens, HIRA-interacting 0 protein 3,clone MGC: 1814 IMAGE: 3345739, mRNA, complete cds 10858I:2458933:04B01:E04 X97544 H. sapiens mRNA for TIM17 8.7E−62 preproteintranslocase 1261 M00023419C:B06 U89606 Human pyridoxal kinase mRNA, 0complete cds 4156 2243-4 X93334 Homo sapiens mitochondrial DNA, 0complete genome 3452 2243-1 X93334 Homo sapiens mitochondrial DNA, 0complete genome 2748 2242-6 X93334 Homo sapiens mitochondrial DNA, 0complete genome 2046 2248-3 X93334 Homo sapiens mitochondrial DNA, 0complete genome 2044 2242-4 X93334 Homo sapiens mitochondrial DNA, 0complete genome 1342 2248-2 X93334 Homo sapiens mitochondrial DNA, 0complete genome 1326 2244-3 X93334 Homo sapiens mitochondrial DNA, 0complete genome 9981 I:1720149:06A01:G09 AF069604 Homo sapiens myosinlight chain 0 kinase isoform 4 (MLCK) mRNA, partial cds 27917035JN002.H04 XM_015978 Homo sapiens hypothetical protein 1.8E−92FLJ22969 (FLJ22969), mRNA 8488 I:1808529:05B01:D01 AJ293647 Homo sapienspartial IL4RA gene 1.1E−125 for interleukin-4 receptor alfa chain, exon11, ECSSQV allele 22793 M00057283C:D06 AF161410 Homo sapiens HSPC292mRNA, 0 partial cds 26883 035JN005.C03 AF161410 Homo sapiens HSPC292mRNA, 0 partial cds 11540 I:1909488:10B01:B11 XM_027739 Homo sapiensduodenal 0 cytochrome b (FLJ23462), mRNA 17707 I:489882:14A01:F02 X99474H. sapiens mRNA for chloride 0 channel, CIC-6c 20649 NIH50_41452 Z14136H. sapiens gene for 0 spermidine/spermine N1- acetyltransferase 24004M00056163C:H09 AF107495 Homo sapiens FWP001 and 0 putative FWP002 mRNA,complete cds 11836 I:1806769:01B02:F11 X93036 H. sapiens mRNA for MAT8protein 0 24932 M00054963C:C09 M26152 Homo sapiens serum amyloid A 0(SAA) mRNA, complete cds 19143 RG:149960:10006:D04 AK003448 Mus musculus18 days embryo 8.9E−21 cDNA, RIKEN full-length enriched library, clone:1110004P15, full insert sequence 26257 035JN013.B08 J04056 Humancarbonyl reductase mRNA, 0 complete cds 21239 M00054679B:B03 J02619Human Z type alpha-1-antitrypsin 0 gene, complete cds (exons 2-5) 16959I:1426031:14B01:B07 AY035783 Homo sapiens laminin 5 beta 3 3.8E−121subunit (LAMB3) mRNA, complete cds 2568 M00022158D:C11 XM_036609 Homosapiens laminin, beta 3 0 (nicein (125 kD), kalinin (140 kD), BM600 (125kD)) (LAMB3), mRNA 25936 035JN020.A07 XM_036608 Homo sapiens laminin,beta 3 0 (nicein (125 kD), kalinin (140 kD), BM600 (125 kD)) (LAMB3),mRNA 23041 M00054797C:G10 XM_046649 Homo sapiens nuclear factor of 0kappa light polypeptide gene enhancer in B-cells inhibitor, alpha(NFKBIA), mRNA 9206 I:1822716:05B01:C08 BC008059 Homo sapiens, clone 0IMAGE: 2967491, mRNA 25105 M00054824C:H04 BC009110 Homo sapiens, cloneMGC: 17355 0 IMAGE: 3453825, mRNA, complete cds 24779 M00057061D:G0722451 M00043372B:B06 X00947 Human alpha 1-antichymotrypsin 0 genefragment 22291 M00054785D:G05 X00947 Human alpha 1-antichymotrypsin 0gene fragment 21143 M00055146A:D11 24751 M00054676B:D07 X03083 Humanlactate dehydrogenase-A 0 gene exon 7 and 3′ flanking region 24294M00056163D:E01 X03083 Human lactate dehydrogenase-A 9.4E−110 gene exon 7and 3′ flanking region 24006 M00056163D:E01 X03083 Human lactatedehydrogenase-A 0 gene exon 7 and 3′ flanking region 25678 035Jn031.H01AK001670 Homo sapiens cDNA FLJ10808 fis, 4.9E−53 clone NT2RP4000879,weakly similar to UBIQUITIN-ACTIVATING ENZYME E1 22027 M00056534C:E08XM_003512 Homo sapiens amphiregulin 0 (schwannoma-derived growth factor)(AREG), mRNA 29495 035JN022.E12 D83761 Homo sapiens mRNA for mother 0against dpp (Mad) related protein, complete cds 24577 M00056654B:G02XM_038306 Homo sapiens dual specificity 0 phosphatase 6 (DUSP6), mRNA23527 M00055865C:D04 17090 I:341491:13B01:A01 BC004490 Homo sapiens,v-fos FBJ murine 3.8E−98 osteosarcoma viral oncogene homolog, clone MGC:11074 IMAGE: 3688670, mRNA, complete cds 25137 M00057167A:C07 23772M00056360A:E07 BC004490 Homo sapiens, v-fos FBJ murine 0 osteosarcomaviral oncogene homolog, clone MGC: 11074 IMAGE: 3688670, mRNA, completecds 1659 M00001350B:D10 BC004490 Homo sapiens, v-fos FBJ murine 0osteosarcoma viral oncogene homolog, clone MGC: 11074 IMAGE: 3688670,mRNA, complete cds 8497 I:2170638:05A01:A07 BC006169 Homo sapiens,Similar to SH3- 5.2E−125 domain binding protein 5 (BTK- associated),clone MGC: 13234 IMAGE: 4025362, mRNA, complete cds 25272 M00054621A:D09AF161435 Homo sapiens HSPC317 mRNA, 0 partial cds 21216 M00056194B:G06XM_002844 Homo sapiens procollagen-lysine, 0 2-oxoglutarate5-dioxygenase (lysine hydroxylase) 2 (PLOD2), mRNA 11939I:2938757:02A02:B05 D43767 Human mRNA for chemokine, 0 complete cds 9191I:1421929:05A01:D02 X63629 H. sapiens mRNA for p cadherin 2.4E−90 34292024-3 AF002697 Homo sapiens E1B 19K/Bcl-2- 0 binding protein Nip3 mRNA,nuclear gene encoding mitochondrial protein, complete cds 2725 2024-1AF002697 Homo sapiens E1B 19K/Bcl-2- 0 binding protein Nip3 mRNA,nuclear gene encoding mitochondrial protein, complete cds 19923I:1001356:13A01:B11 BC006318 Homo sapiens, erythrocyte 1.7E−103 membraneprotein band 4.9 (dematin), clone MGC: 12740 IMAGE: 4125804, mRNA,complete cds 20457 I:1923289:19A01:E06 XM_035603 Homo sapiens gapjunction protein, 0 beta 5 (connexin 31.1) (GJB5), mRNA 24773M00057055D:B11 24119 M00042886D:H10 BC006260 Homo sapiens, Similar toN-myc 4.4E−114 downstream regulated, clone MGC: 11293 IMAGE: 3946764,mRNA, complete cds 3908 M00027080A:E06 M60756 Human histone H2B.1 mRNA,3′ 0 end 8560 I:2346704:06B01:H01 AJ000334 Homo sapiens mRNA forcytosolic 0 asparaginyl-tRNA synthetase 24588 M00055411A:C10 L19779 Homosapiens histone H2A.2 0 mRNA, complete cds 4047 M00007997C:B08 XM_009091Homo sapiens glycogen synthase 0 1 (muscle) (GYS1), mRNA 28344035JN011.E11 XM_050471 Homo sapiens glycogen synthase 0 1 (muscle)(GYS1), mRNA 27561 035JN001.F04 XM_001472 Homo sapiens v-jun aviansarcoma 0 virus 17 oncogene homolog (JUN), mRNA 3272 M00022165C:E12NM_001024 Homo sapiens ribosomal protein 0 S21 (RPS21), mRNA 26735035JN030.A08 XM_010408 Homo sapiens RAB9-like protein 0 (RAB9L), mRNA24900 M00054500D:C08 BC004427 Homo sapiens, proteasome 0 (prosome,macropain) subunit, alpha type, 7, clone MGC: 3755 IMAGE: 2819923, mRNA,complete cds 9472 I:2510171:04B01:H08 X04503 Human SLPI mRNA fragmentfor 0 secretory leucocyte protease inhibitor 9979 I:1623318:06A01:F09L31409 Homo sapiens creatine transporter 2.2E−45 mRNA, complete cds21996 M00042467B:B04 L00160 Human phosphoglycerate kinase 0 (pgk) mRNA,exons 2 to last 22312 M00055035D:F05 11327 I:3139773:05A01:H11 L00160Human phosphoglycerate kinase 2.6E−21 (pgk) mRNA, exons 2 to last 18240RG:1927470:10015:H08 V00572 Human mRNA encoding 0 phosphoglyceratekinase 21922 M00054848A:D12 AF139065 Homo sapiens desmoplakin I 0 mRNA,partial cds 22290 M00057002D:H01 10390 I:1405391:03B02:C09 AF056979 Homosapiens clone YAN1 0 interferon-gamma receptor mRNA, complete cds 2212M00008098B:F06 U19247 Homo sapiens interferon-gamma 0 receptor alphachain gene, exon 7 and complete cds 20213 RG:221172:10007:C11 S74774p59fyn(T) = OKT3-induced calcium 2.9E−103 influx regulator [human,Jurkat J6 T cell line, mRNA Partial, 1605 nt] 24955 M00055929D:D04 19574I:635178:13B02:C10 XM_033944 Homo sapiens superoxide 0 dismutase 2,mitochondrial (SOD2), mRNA 19969 RG:501476:10010:A05 U14394 Human tissueinhibitor of 0 metalloproteinases-3 mRNA, complete cds 8570I:1696224:06B01:E07 X70684 C. aethiops mRNA for heat shock 5.6E−25protein 70 18519 I:1997703:13A01:D09 X52947 Human mRNA for cardiac gap 0junction protein 9616 I:3200341:06B02:H02 Y00106 Human gene forbeta-adrenergic 0 receptor (beta-2 subtype) 22334 M00055067D:H12 17459I:2056395:13A02:B07 M77349 Human transforming growth factor- 2.5E−121beta induced gene product (BIGH3) mRNA, complete cds 25193M00056763B:A12 X68277 H. sapiens CL 100 mRNA for 0 protein tyrosinephosphatase 25191 M00056763B:A12 X68277 H. sapiens CL 100 mRNA for 0protein tyrosine phosphatase 9448 I:2455617:04B01:D02 XM_051799 Homosapiens guanosine 0 monophosphate reductase (GMPR), mRNA 25224RG:950682:10003:D06 BC002536 Homo sapiens, 0 phosphofructokinase,platelet, clone MGC: 2192 IMAGE: 3140233, mRNA, complete cds 20218RG:2158297:10016:E11 BC002536 Homo sapiens, 0 phosphofructokinase,platelet, clone MGC: 2192 IMAGE: 3140233, mRNA, complete cds 3089NIH50_26184 D25328 Human mRNA for platelet-type  2E−108phosphofructokinase, complete cds 23985 NIH50_26184 19953 NIH50_26184D25328 Human mRNA for platelet-type  2E−108 phosphofructokinase,complete cds 11506 NIH50_26184 22362 M00056349A:F08 M10546 Humanmitochondrial DNA, 1.2E−86 fragment M1, encoding transfer RNAs,cytochrome oxidase I, and 2 URFs 25516 035JN011.G01 XM_011470 Homosapiens myristoylated 0 alanine-rich protein kinase C substrate (MARCKS,80K-L) (MACS), mRNA 25757 037XN005.H07 AF017116 Homo sapiens type-2phosphatidic 0 acid phosphohydrolase (PAP2) mRNA, complete cds 24814M00042773B:E09 M17733 Human thymosin beta-4 mRNA, 0 complete cds 21994M00042465B:E04 M17733 Human thymosin beta-4 mRNA, 0 complete cds 27117037XN001.H03 BC001631 Homo sapiens, prothymosin beta 4, 0 clone MGC:2219 IMAGE: 3536637, mRNA, complete cds 24681 NIH50_41452 22745M00056592A:B08 NM_003739 Homo sapiens aldo-keto reductase 0 family 1,member C3 (3-alpha hydroxysteroid dehydrogenase, type II) (AKR1C3), mRNA24233 M00055873C:B06 2001 M00001381A:F03 XM_035387 Homo sapiensribosomal protein, 0 large, P1 (RPLP1), mRNA 21179 NIH50_43550 17147NIH50_43550 AK026515 Homo sapiens cDNA: FLJ22862 0 fis, clone KAT01966,highly similar to HSLDHAR Human mRNA for lactate dehydrogenase-A 8700NIH50_43550 21214 M00056193B:D06 BC006260 Homo sapiens, Similar to N-myc0 downstream regulated, clone MGC: 11293 IMAGE: 3946764, mRNA, completecds 26422 037XN003.D08 BC006260 Homo sapiens, Similar to N-myc 0downstream regulated, clone MGC: 11293 IMAGE: 3946764, mRNA, completecds 22837 M00055891C:B09 21965 M00057029A:G09 25541 035JN013.D01AK026310 Homo sapiens cDNA: FLJ22657 0 fis, clone HSI07791, highlysimilar to HUMCYB5 Human cytochrome b5 mRNA 18302 I:1738248:09B02:G08XM_016114 Homo sapiens hypothetical protein 0 FLJ22501 (FLJ22501), mRNA24049 M00054706B:G04 AF107495 Homo sapiens FWP001 and 0 putative FWP002mRNA, complete cds 26326 035JN023.D08 AK025906 Homo sapiens cDNA:FLJ22253 0 fis, clone HRC02763 2254 M00004085C:C02 AK025703 Homo sapienscDNA: FLJ22050 0 fis, clone HEP09454 10296 I:2868216:07B02:D09 AK025703Homo sapiens cDNA: FLJ22050 0 fis, clone HEP09454 20044I:2547084:09B01:F05 XM_016847 Homo sapiens hypothetical protein 0FLJ22002 (FLJ22002), mRNA 28806 035JN028.D05 AK025504 Homo sapiens cDNA:FLJ21851 0 fis, clone HEP01962 17566 I:446969:17B02:G07 AK023217 Homosapiens cDNA FLJ13155 fis,  2E−115 clone NT2RP3003433 19005I:2674167:09A02:G09 AK022968 Homo sapiens cDNA FLJ12906 fis, 0 cloneNT2RP2004373 3567 M00023369D:C05 21983 M00057081B:H03 458 M00022134B:E08XM_037412 Homo sapiens hypothetical gene 0 supported by BC008993(LOC91283), mRNA 22331 M00057138A:E11 21411 M00055833D:B03 22972M00056956D:B01 24533 RG:1643392:10014:C11 24853 M00056617D:F07 AK020869Mus musculus adult retina cDNA, 6.5E−59 RIKEN full-length enrichedlibrary, clone: A930017A02, full insert sequence 23753 M00054915A:G0221502 M00056193B:D06 18180 RG:39422:10005:B02 23918 M00056278C:E03 24144RG:1982961:20001:H05 19996 RG:1283072:10012:F11 BC009107 Homo sapiens,clone MGC: 17352 0 IMAGE: 3449913, mRNA, complete cds 11528I:1899534:10B01:D05 20506 I:1969044:18B01:E12 AB048286 Homo sapiensGS1999full mRNA, 0 complete cds 23833 RG:1656861:10014:E10 20042I:1873176:09B01:E05 BC001909 Homo sapiens, clone 0 IMAGE: 3537447, mRNA,partial cds 24977 M00055820D:F01 11646 I:1723142:08B02:G11 AK014612 Musmusculus 0 day neonate skin 4.6E−45 cDNA, RIKEN full-length enrichedlibrary, clone: 4633401I05, full insert sequence 24872RG:773612:10011:D06 10577 I:2174196:08A01:A10 21710 RG:1091554:10003:G0118556 RG:31082:10004:F09 29433 035JN014.F12 AK001805 Homo sapiens cDNAFLJ10943 fis, 0 clone OVARC1001360 29273 037XN005.F12 28763 035JN018.G11AJ310543 Homo sapiens mRNA for EGLN1 1.9E−40 protein 27887RG:2364147:8119908:A10 27450 035JN032.F09 27255 035JN006.E09 XM_027456Homo sapiens hypothetical gene 1.2E−57 supported by AK000584 (LOC89942),mRNA 27226 035JN004.F09 26550 035JN008.D08 26508 035JN004.G02 26483RG:2377371:8119908:C08 26334 035JN023.H08 AF364547 Homo sapiensmethylmalonyl-CoA 0 epimerase mRNA, complete cds; nuclear gene formitochondrial product 26027 035JN030.G01 25977 035JN022.F07 25965035JN022.H01 25844 035JN008.C07 25834 035JN008.F01 AB048289 Bos tauruslae mRNA for lipoate- 3.1E−35 activating enzyme, complete cds 25816035JN004.E07 25746 037XN007.B07 25742 037XN007.H01 25741 037XN005.H0125712 037XN003.A07 25642 035Jn027.F01 25621 035JN021.D07 AK027321 Homosapiens cDNA FLJ14415 fis, 0 clone HEMBA1004889, weakly similar to HumanC3f mRNA 25614 035JN023.H01 25603 035JN021.C01 25556 035JN015.C07 25555035JN013.C07 25540 035JN015.C01 23576 RG:1984769:20002:D10 22566RG:1996656:20003:C03 9036 DD182 4164 M00007932B:E06 4146 2179-5 4091M00026845A:E01 4072 M00023398A:G12 4022 M00022127D:B06 3965M00005406A:f04 3954 M00005400B:E1 3872 M00007974D:B04 3869M00003868C:A03 3838 M00007052A:C09 XM_048272 Homo sapiens similar toRas- 0 related GTP-binding protein (H. sapiens) (LOC92951), mRNA 38062168-2 3798 2138-4 3792 2171-5 3788 2156-4 3767 M00001355D:H12 3458M00007160D:E10 3251 M00005471A:a04 3194 DF821 3102 2167-1 3094 2138-32671 M00023431A:D02 2634 M00008025D:A04 2567 M00008061B:A12 2317M00001502D:E09 1958 M00023296B:B09 1680 2169-5 1625 M00001542C:G08 1445M00023335C:C09 1320 2207-5 974 2161-1 726 DO15 718 ER418 703M00004189D:A11 652 M00007070A:C08 630 2203-2 593 M00001373A:A06 X93036H. sapiens mRNA for MAT8 protein 0 532 M00022005A:H05 272 2168-5 256M00001406C:H12 57 M00023371B:H02

TABLE 19 3D T4-2/ SEQ ID SPOT 2D T4-2/ 3D T4-2/ 3D S1/ 3D T4-2/ 3D T4-2/B1 Integrin 3D T4-2/ NO. ID 2D S1 3D S1 2D S1 2D T4-2 EGFR Ab Ab Tyr2506 10594 0.6 2.2 0.6 1.9 3.0 1.0 2.9 2507 21851 1.0 1.0 1.0 3.5 1.31.0 1.0 2508 20990 1.6 4.6 1.0 1.5 1.0 1.0 1.0 2509 18641 1.0 0.6 2.61.7 1.0 1.6 1.0 2510 17229 0.3 0.8 1.0 2.1 1.0 1.0 1.0 2511 25930 1.01.0 1.0 1.0 1.0 1.0 1.0 2512 20701 1.6 2.9 1.3 2.7 4.5 1.9 5.8 251320346 1.7 2.7 1.4 2.6 4.3 2.0 5.2 2514 21247 1.0 4.4 1.5 3.0 3.4 2.6 4.72515 23062 0.6 2.5 0.6 1.8 3.3 1.4 2.7 2516 25666 1.0 2.9 0.6 2.0 3.61.0 2.3 2517 19001 8.5 14.2 1.0 1.0 4.8 1.7 8.0 2518 10897 1.0 3.1 4.51000.0 13.3 4.6 18.4 2519 1960 0.3 1.5 3.0 13.7 3.9 2.4 4.9 2520 263811.0 1.0 1.0 0.9 1.0 1.0 1.0 2521 26719 0.4 1.0 0.6 2.8 1.2 1.7 1.0 252227152 4.2 3.0 2.2 1.5 1.3 1.0 1.3 2523 10926 0.7 1.9 0.9 2.1 3.7 1.5 3.32524 28980 0.6 1.4 1.0 2.4 1.0 1.0 1.0 2525 1236 1.0 2.8 0.8 2.1 2.2 1.83.2 2526 29350 0.5 0.6 1.2 2.1 1.4 1.0 1.0 2527 26242 1.0 1.0 0.6 2.21.0 1.0 2.0 2528 4098 1.4 3.9 0.6 2.1 2.7 1.3 3.1 2529 17432 0.4 0.3 2.42.1 0.3 0.9 0.3 2530 1785 0.5 0.4 2.4 2.0 0.3 1.0 0.3 2531 28856 8.5 0.92.5 0.3 0.6 1.0 0.5 2532 18791 1.0 0.2 0.3 4.1 1.0 1.0 1.3 2533 229503.9 4.1 1.2 1.0 2.1 1.0 2.4 2534 1882 2.4 4.1 0.9 1.8 3.2 1.5 4.7 253523886 1.0 1.0 1.2 2.1 1.0 1.0 1.0 2536 24995 2.0 1.6 2.1 1.0 1.0 1.0 1.02537 24477 1.0 1.9 1.0 4.2 2.7 1.3 1.8 2538 21681 1.7 7.1 0.6 2.0 2.81.0 3.6 2539 9557 1.6 7.5 0.8 1.0 3.0 1.0 2.5 2540 22033 2.8 3.7 1.0 0.92.2 1.0 2.7 2541 873 1.0 4.0 1.0 2.7 1.7 1.0 1.0 2542 17144 1.0 0.5 3.61.4 1.0 1.0 1.0 2543 26970 6.0 15.3 0.2 0.6 2.9 1.0 5.4 2544 21402 0.21.0 2.8 6.9 2.4 1.0 3.6 2545 27074 1.7 2.5 2.3 3.2 1.6 1.0 2.0 254610963 0.5 0.3 2.1 0.5 1.0 1.0 0.7 2547 29525 0.6 1.0 0.7 2.4 1.7 1.3 1.02548 25514 1000.0 1.0 1.0 1.0 0.5 1.0 1.0 2549 26612 0.4 0.5 1.6 2.8 0.81.0 0.8 2550 24600 1.6 2.7 1.0 2.0 1.0 1.2 1.4 2551 9741 2.3 5.0 1.0 2.21.7 1.0 1.0 2552 23689 1.0 2.6 0.8 1.8 2.3 1.0 2.7 2553 22352 1.0 2.90.7 1.6 2.4 1.0 2.4 2554 23806 1.0 0.4 1.3 2.3 1.0 1.4 1.4 2555 122851.0 1.0 1.0 1.0 0.8 1.0 0.5 2556 27638 0.6 1.0 0.8 2.2 2.1 1.0 1.0 25579663 1.0 1.0 1.0 1000.0 1.0 1.0 1.0 2558 26850 1.0 0.2 9.1 2.1 1.3 1.62.2 2559 10204 2.9 2.3 0.8 0.6 3.1 1.4 2.4 2560 1318 2.0 0.9 2.3 0.5 0.61.1 0.7 2561 25922 1.0 0.8 1.0 1.0 1.0 1.0 1.0 2562 26347 1.0 1.0 1.01.0 1.0 1.0 1.0 2563 20361 1.0 1.0 1.0 2.0 1.0 1.0 1.0 2564 28672 0.62.1 0.6 2.1 1.4 1.0 1.7 2565 25520 0.5 0.3 2.3 1.3 1.0 0.7 0.5 2566 17231.0 0.5 5.1 3.5 1.0 3.1 1.0 2567 28863 0.8 1.3 1.0 2.3 1.7 1.7 1.7 256825526 5.9 1.7 1.0 0.6 0.6 0.7 0.4 2569 27936 1.0 1.0 3.2 3.1 1.9 3.1 1.52570 26851 1.0 0.7 3.2 2.7 1.6 2.4 1.3 2571 25107 1.0 5.8 1.0 2.6 2.61.6 2.6 2572 24912 1.0 2.9 1.0 2.4 1.6 1.3 1.8 2573 25169 1.0 0.7 2.51.5 1.0 1.0 1.0 2574 25600 1.6 1.4 2.9 2.1 0.7 0.9 0.5 2575 28706 0.20.5 0.6 2.1 1.3 1.2 1.0 2576 26377 0.6 0.3 2.2 1.0 1.2 1.3 1.0 257719460 2.4 1.5 2.5 1.3 1.0 1.0 0.8 2578 25243 1.0 0.7 2.2 1.0 1.0 1.0 1.02579 20018 1.0 1.0 1.0 2.6 1.0 1.0 1.0 2580 918 1.0 1.7 1.3 2.1 2.0 1.62.4 2581 25027 1.0 1.0 1.0 1.0 1.0 1.0 1.0 2582 29089 0.6 0.5 0.8 2.11.0 1.0 1.0 2583 9141 1.0 1.0 1.0 1.0 1.0 1.0 1.0 2584 12005 1.0 1.0 2.21.0 1.0 1.0 1.0 2585 12148 1.0 1.0 1.0 1.0 1.0 1.0 1.0 2586 17394 0.40.6 2.1 2.0 1.0 1.0 1.0 2587 27017 2.8 3.3 0.8 1.0 2.4 1.8 2.8 258825809 1.0 1.0 1000.0 1.0 1.0 1.0 1.0 2589 8719 0.1 1.0 2.3 2.1 0.4 0.50.3 2590 21030 0.4 1.0 1.3 2.1 1.4 1.6 1.4 2591 11436 0.7 0.4 2.0 1.00.6 0.8 0.6 2592 10374 1.5 1.5 3.5 2.7 0.4 1.0 0.3 2593 19037 3.0 3.30.9 1.5 2.7 1.4 3.7 2594 398 1.6 6.9 1.1 3.3 2.4 1.0 4.5 2595 18773 1.95.1 1.0 3.9 3.8 2.0 6.1 2596 3583 0.5 0.7 1.0 2.0 2.5 1.0 1.5 2597 34181.8 3.2 1.2 2.4 1.6 1.0 1.2 2598 18985 9.2 3.1 1.0 0.6 2.3 1.1 2.5 259925861 3.4 1.5 2.0 0.8 0.8 0.9 0.6 2600 3317 0.9 2.3 1.0 3.4 1.9 1.0 1.02601 8743 0.2 0.7 1.0 4.3 1.8 1.0 1.7 2602 26240 0.2 1.0 1.0 5.3 1.9 1.91.1 2603 28562 0.3 0.2 2.0 1.0 0.5 0.5 0.6 2604 16877 1.0 2.6 1.1 2.61.7 1.5 1.3 2605 25955 1.0 1.0 1.0 1.0 1.0 1.0 1.0 2606 26308 0.2 0.41.0 2.2 0.7 0.8 0.6 2607 4140 1.9 6.7 0.7 2.1 3.0 1.0 3.5 2608 3436 1.86.3 0.6 2.2 3.1 1.3 3.3 2609 25612 1.0 12.5 1.0 1.0 2.1 1.0 2.9 261012257 1.0 1.0 2.0 1.0 0.8 0.9 0.8 2611 9111 0.5 0.5 2.2 1.3 1.5 1.0 0.72612 17620 0.3 0.8 1.0 3.2 2.7 2.1 1.0 2613 26025 1.0 2.9 1.1 2.2 2.31.0 2.6 2614 19271 0.5 1.3 0.7 2.2 1.6 1.2 1.5 2615 4151 0.4 4.2 1.211.1 4.2 1.0 2.9 2616 26569 0.7 2.2 0.8 2.9 2.3 1.7 2.6 2617 10344 1.01.0 1.0 1.0 1.0 1.0 1.0 2618 832 1.0 3.3 1.0 2.4 3.7 2.2 4.0 2619 120711.8 1.5 2.2 1.0 1.3 0.8 1.4 2620 12271 0.6 4.9 1.9 14.9 20.8 4.0 24.12621 11433 0.5 0.4 5.7 3.0 1.7 1.8 1.0 2622 20917 1.0 2.8 0.9 2.6 1.71.4 1.7 2623 25810 1.1 3.8 1.0 2.9 1.5 1.3 1.5 2624 12039 1.0 1.0 3.61.0 1.0 1.0 1.0 2625 25499 1.0 1.0 1.0 1.0 1.0 1.0 1.0 2626 25557 1.01.8 1.0 0.8 1.0 1.0 1.0 2627 9917 2.5 2.7 0.7 1.6 3.8 1.2 3.6 2628 195050.4 1.7 0.7 3.8 1.7 1.6 1.4 2629 17491 0.6 1.7 0.7 2.5 1.6 1.3 1.4 263010683 0.4 1.9 0.6 3.6 1.7 1.4 1.1 2631 1936 0.2 0.6 0.6 3.1 1.0 1.8 1.02632 828 0.1 1.0 0.5 3.0 1.0 1.7 1.2 2633 9558 1.0 1.0 1.0 1.0 1.0 1.01.0 2634 20164 2.0 1.1 2.5 1.7 1.0 1.0 0.8 2635 969 1.0 1.0 2.7 1.0 1.01.5 0.7 2636 9910 0.4 1.0 0.8 3.2 1.9 1.3 1.4 2637 2427 1.3 0.7 3.0 2.80.8 1.9 1.0 2638 19990 1.0 7.9 2.8 34.7 1.0 1.0 1.0 2639 20605 3.0 1.22.1 1.0 1.3 1.2 0.8 2640 10650 0.5 1.7 0.5 2.9 2.8 0.6 3.4 2641 259632.6 3.5 0.7 1.0 3.3 1.0 2.3 2642 25562 3.2 5.9 0.7 1.0 4.2 1.0 4.8 26439377 0.6 1.0 1.0 2.1 1.9 2.0 1.6 2644 17618 1.0 0.7 2.3 3.2 0.8 0.7 0.82645 12136 1.0 1.0 3.8 1.0 1.0 1.0 1.0 2646 17373 1.0 0.4 6.1 2.4 1.01.0 1.0 2647 18577 1.0 0.3 0.3 4.6 1.0 1.0 1.0 2648 3143 1.7 1.3 2.6 2.30.7 1.0 0.5 2649 17737 6.1 0.7 3.4 0.3 0.5 1.3 0.4 2650 20029 1.0 0.62.3 1.0 1.0 1.0 0.5 2651 18537 1.0 1.3 2.1 2.6 1.3 1.0 1.2 2652 100901.0 1.7 2.1 2.8 1.5 1.0 1.2 2653 12102 1.0 1.0 3.9 1.0 1.0 1.0 1.0 26548487 4.7 2.4 1.0 1.0 2.3 1.1 2.2 2655 9252 1.3 3.8 0.3 1.0 2.1 1.6 2.52656 25605 1.0 1.0 1.0 1.0 0.5 0.5 1.0 2657 29652 1.0 2.9 1.5 2.9 2.01.5 2.1 2658 10858 1.0 0.8 2.0 1.0 1.0 1.0 0.7 2659 1261 0.2 0.6 1.0 2.90.8 0.8 0.9 2660 4156 12.4 0.8 3.1 0.2 0.6 1.0 0.3 2661 3452 10.6 0.82.8 0.3 0.6 1.0 0.4 2662 2748 10.8 0.8 3.1 0.2 0.5 1.0 0.4 2663 2046 9.21.0 2.4 0.3 0.5 1.2 0.4 2664 2044 11.7 0.8 2.8 0.2 0.6 1.4 0.4 2665 134210.5 0.9 2.8 0.2 0.5 1.2 0.4 2666 1326 12.2 1.0 2.7 0.2 0.5 1.0 0.4 26679981 0.2 1.5 0.3 2.5 1.2 1.6 0.5 2668 27917 1.9 2.5 0.5 1.0 2.1 1.4 2.32669 8488 4.3 2.4 1.0 0.5 2.9 0.9 3.6 2670 22793 1.9 2.6 0.5 1.0 2.2 1.82.1 2671 26883 2.4 3.7 0.5 1.0 2.5 2.0 2.0 2672 11540 0.7 1.0 1.3 2.80.8 1.0 0.5 2673 17707 1.0 0.6 2.6 1.0 1.0 1.0 1.0 2674 20649 2.3 2.60.5 0.4 3.0 1.0 3.1 2675 24004 1.0 2.5 1.8 3.6 2.3 1.0 2.8 2676 118361.2 5.0 0.9 3.7 1.3 1.0 0.8 2677 24932 1.8 0.8 6.5 2.1 0.8 1.0 0.5 267819143 0.6 1.6 0.7 2.0 1.7 1.2 1.4 2679 26257 1.9 1.3 2.2 1.7 0.7 1.0 0.62680 21239 9.4 9.2 0.5 0.4 2.4 1.0 2.7 2681 16959 0.6 2.1 0.8 2.1 3.01.4 2.5 2682 2568 0.7 1.9 0.7 2.2 3.0 1.3 2.4 2683 25936 1.0 2.4 0.7 2.03.1 1.5 2.4 2684 23041 0.7 1.0 2.1 2.6 1.0 1.4 1.0 2685 9206 5.7 1.8 4.61.0 1.0 0.7 0.9 2686 25105 1.6 1.3 2.1 1.0 1.0 0.7 0.8 2687 24779 1.01.0 1.0 2.9 2.3 1.4 1.2 2688 22451 1.0 0.2 2.1 1.0 1.4 0.6 1.0 268922291 0.2 0.2 2.1 1.0 0.6 0.6 0.5 2690 21143 1.0 7.2 0.7 2.0 2.6 1.1 2.42691 24751 1.7 5.0 0.7 2.1 2.4 1.3 4.0 2692 24294 1.7 3.9 0.8 2.4 2.61.1 3.9 2693 24006 1.7 6.3 0.8 2.5 2.4 1.0 4.0 2694 25678 1.0 1.0 1.01.0 1.0 1.0 1.0 2695 22027 8.7 7.0 0.4 0.2 5.1 2.0 5.2 2696 29495 1.01.0 1.0 1.0 1.0 1.0 1.0 2697 24577 6.8 3.2 0.8 0.4 3.8 1.3 2.1 269823527 0.3 2.1 1.6 6.4 2.7 2.1 3.4 2699 17090 1.0 4.9 0.7 2.3 3.1 2.3 3.62700 25137 1.0 1.0 0.4 3.8 1.0 2.5 4.1 2701 23772 0.6 6.8 0.5 3.7 12.63.6 9.2 2702 1659 1.0 7.5 0.3 3.2 17.8 4.1 20.3 2703 8497 1.3 0.4 2.20.5 1.0 1.0 1.0 2704 25272 8.0 6.0 1.0 0.6 2.2 1.0 2.9 2705 21216 1.01.0 0.6 2.0 2.5 2.0 2.2 2706 11939 1.0 1.0 1.0 1.0 1.0 1.0 1.0 2707 91911.8 2.2 1.3 1.1 2.2 1.0 2.0 2708 3429 0.7 3.4 0.8 3.5 3.0 1.5 3.7 27092725 0.8 3.4 1.0 3.4 2.6 1.6 4.1 2710 19923 1.0 1.1 2.9 1.0 1.7 1.4 1.22711 20457 1.0 2.0 1.0 2.3 2.9 1.0 2.3 2712 24773 0.2 1.0 0.8 2.0 1.61.0 1.0 2713 24119 0.2 4.6 1.1 15.9 2.7 1.0 3.4 2714 3908 0.3 0.5 1.12.3 1.7 1.0 1.0 2715 8560 1.9 0.7 2.2 0.5 1.0 1.0 0.7 2716 24588 0.3 0.51.0 2.0 1.0 1.0 1.4 2717 4047 0.5 1.2 1.0 2.1 1.9 1.0 1.8 2718 28344 0.81.0 1.0 2.0 1.7 1.5 2.7 2719 27561 1.0 1.0 1.0 2.4 1.2 1.2 1.3 2720 32720.6 0.8 1.0 2.1 1.3 1.6 1.0 2721 26735 1.0 1.0 1.0 1.0 1.0 1.0 1.0 272224900 0.3 0.8 2.9 5.7 2.2 1.1 3.0 2723 9472 2.2 5.0 1.0 2.0 1.5 0.8 1.72724 9979 1.3 3.3 1.5 3.9 3.4 1.4 2.5 2725 21996 1.0 4.7 1.0 3.4 2.5 1.02.4 2726 22312 1.2 4.4 1.2 3.3 2.2 1.1 2.2 2727 11327 1.4 6.2 1.4 2.72.7 1.0 2.2 2728 18240 2.0 4.5 1.0 2.2 2.1 1.0 2.7 2729 21922 0.7 1.40.8 2.1 1.8 1.0 1.3 2730 22290 0.7 1.6 0.9 2.1 1.5 1.2 1.3 2731 103901.3 1.0 2.6 1.6 0.8 1.0 0.6 2732 2212 1.9 1.0 2.8 1.0 0.6 1.6 0.8 273320213 0.4 1.0 1.0 1.0 1.0 1.0 1.0 2734 24955 0.9 2.9 1.0 3.3 0.8 0.8 1.02735 19574 1.0 0.6 3.7 3.1 1.5 2.6 1.4 2736 19969 1.0 1.0 1.0 3.1 1.01.0 1.0 2737 8570 0.4 1.2 1.0 2.6 1.2 0.8 0.6 2738 18519 3.5 2.9 2.6 1.81.8 1.0 2.0 2739 9616 0.6 2.0 1.0 2.3 1.2 1.2 1.0 2740 22334 0.2 0.7 2.98.5 1.7 1.1 3.4 2741 17459 0.1 0.7 2.7 18.8 4.0 1.3 4.6 2742 25193 1.00.8 1.0 2.3 1.0 1.3 1.0 2743 25191 0.2 0.8 0.7 2.5 1.3 1.5 1.2 2744 94480.6 1.0 1.0 2.3 0.8 0.8 0.5 2745 25224 5.6 14.4 1.0 2.3 6.0 1.5 9.6 274620218 6.1 12.3 0.7 1.7 5.6 1.6 9.0 2747 3089 7.0 15.7 0.7 2.3 7.3 1.88.0 2748 23985 5.8 17.2 0.9 2.1 6.8 1.8 8.1 2749 19953 6.2 13.5 0.8 1.86.4 1.7 10.4 2750 11506 4.1 13.3 1.0 1.4 4.4 1.6 7.2 2751 22362 1.0 0.74.1 2.1 1.2 1.8 1.0 2752 25516 0.7 10.1 0.4 4.0 14.7 4.7 8.1 2753 257570.6 0.4 2.4 1.0 1.0 1.3 0.9 2754 24814 0.5 2.8 0.3 1.0 3.5 1.4 4.4 275521994 0.5 3.2 0.3 1.0 3.6 1.0 4.3 2756 27117 1.0 2.8 0.3 1.0 3.9 1.0 4.92757 24681 1.8 2.6 0.6 0.5 3.2 1.5 3.0 2758 22745 0.3 2.4 1.4 8.1 2.82.3 3.5 2759 24233 1.9 3.9 1.3 2.3 1.3 0.8 2.2 2760 2001 1.0 1.0 1.5 2.11.0 1.0 1.0 2761 21179 2.0 7.9 0.7 1.9 2.1 1.0 4.3 2762 17147 1.3 4.30.7 1.7 2.4 1.2 3.9 2763 8700 1.5 7.3 0.7 1.6 3.1 1.0 2.7 2764 21214 0.35.4 1.2 15.5 3.1 1.0 3.6 2765 26422 0.4 3.7 1.0 12.7 3.9 1.0 3.3 276622837 0.7 1.0 2.1 2.4 1.2 1.5 0.9 2767 21965 1.0 1.0 1.0 2.2 2.4 1.0 1.02768 25541 4.5 2.7 2.7 0.8 1.0 1.3 0.8 2769 18302 1.1 0.9 2.1 1.0 1.01.0 1.0 2770 24049 1.0 2.6 1.5 2.5 2.3 1.4 2.4 2771 26326 9.2 1.5 3.20.7 0.7 0.9 1.0 2772 2254 1.6 3.3 1.0 2.8 2.0 1.1 3.1 2773 10296 0.9 1.72.9 5.0 2.1 1.0 1.3 2774 20044 1.0 0.8 2.0 1.0 1.0 1.0 1.0 2775 288062.8 1.1 2.1 1.0 0.9 1.2 0.8 2776 17566 7.5 4.2 0.7 0.5 2.5 1.0 2.5 277719005 1.0 0.8 1.0 2.1 1.0 1.0 1.0 2778 3567 1.0 1.0 1.0 1.0 1.0 1.0 1.02779 21983 0.1 1.0 3.1 25.6 3.4 1.0 4.7 2780 458 1.0 2.1 0.6 1.0 1.6 2.12.3 2781 22331 0.6 2.1 0.4 1.0 2.2 1.0 2.8 2782 21411 0.7 1.5 1.0 2.51.0 1.0 1.0 2783 22972 1.0 2.2 0.5 1.0 2.2 1.4 2.4 2784 24533 1.0 2.51.0 2.0 2.0 2.7 3.2 2785 24853 1.0 2.6 2.1 2.1 2.4 1.3 2.1 2786 237530.7 1.5 1.3 2.1 2.0 1.7 2.3 2787 21502 0.3 4.8 1.0 10.8 2.6 1.0 2.9 278818180 0.3 0.8 0.8 2.4 0.9 1.4 0.7 2789 23918 0.7 2.3 0.4 1.0 2.4 1.2 3.52790 24144 1.0 1.0 1.0 1.0 1.0 1.6 1.0 2791 19996 1.5 2.5 0.7 1.2 2.10.9 2.5 2792 11528 1.0 1.0 1.0 2.1 1.0 1.0 1.0 2793 20506 2.2 0.9 3.20.8 1.3 1.6 1.0 2794 23833 1.0 0.5 2.1 1.0 1.0 1.0 0.7 2795 20042 3.81.6 2.3 0.8 1.0 1.0 1.0 2796 24977 1.0 1.0 2.1 1.0 2.3 1.4 1.4 279711646 1.0 1.0 0.8 1000.0 1.0 1.0 1.7 2798 24872 1.0 1.4 0.8 2.5 1.4 1.21.3 2799 10577 1.0 1.0 1.0 1.0 1.0 1.0 1.0 2800 21710 1.0 0.2 2.2 0.71.6 1.0 1.2 2801 18556 0.0 1.0 1.0 1.0 1.0 1.0 1.0 2802 29433 1.0 0.51.0 2.1 1.0 1.0 1.0 2803 29273 1.0 2.2 1.0 2.2 1.0 1.3 1.0 2804 287631.6 2.7 1.0 2.2 1.8 1.3 2.5 2805 27887 0.1 0.2 1.1 2.7 0.8 1.0 0.6 280627450 2.6 11.3 0.2 1.0 4.4 3.3 7.3 2807 27255 0.6 1.6 0.8 2.3 1.7 1.41.5 2808 27226 1.0 1.3 1.0 2.6 1.8 1.0 1.0 2809 26550 4.2 17.9 0.2 1.06.9 2.9 9.2 2810 26508 1.0 1.4 1.0 1.0 1.0 1.0 1.0 2811 26483 1.2 2.20.6 1.0 2.1 1.4 2.7 2812 26334 1.0 0.5 3.0 1.0 0.6 0.8 0.5 2813 260271.0 1.0 1.0 1.5 1.0 1.0 1.0 2814 25977 1.0 1.0 1.0 1.0 1.0 1.0 1.0 281525965 1.0 1.0 1.0 1.0 1.0 1.0 1.0 2816 25844 1.0 1.0 1.0 1.0 1.0 1.0 1.02817 25834 1000.0 1.0 1.0 1.0 0.4 1.0 1.0 2818 25816 1.0 1.0 1.0 1.0 1.01.0 1.0 2819 25746 1.0 1.0 1.0 1.0 1.0 1.0 1.0 2820 25742 1.0 1.0 1.01.0 0.5 1.0 1.0 2821 25741 1.0 1.0 1.0 1.0 1.0 1.0 1.0 2822 25712 1.01.0 1.0 1.0 1.0 1.0 1.0 2823 25642 1.0 1.0 1.0 1.0 1.0 1.0 1.0 282425621 0.6 0.8 2.1 2.0 1.3 1.2 1.0 2825 25614 1.0 1.0 1.0 1.0 1.0 1.0 1.02826 25603 1.0 1.0 1.0 1.0 1.0 1.0 1.0 2827 25556 1.8 0.7 1.0 0.8 1.01.0 1.0 2828 25555 1.0 2.9 1.0 1.0 1.5 1.3 1.0 2829 25540 1.0 1.0 1.01.2 1.0 1.0 1.0 2830 23576 0.0 1.0 1.0 1.0 1.0 1.5 1.4 2831 22566 1.01.0 1.0 1.0 1.0 1.3 1.0 2832 9036 1.9 3.8 0.6 1.8 2.6 1.3 3.1 2833 41641.0 1.0 2.2 1.0 1.5 1.0 0.9 2834 4146 0.8 3.7 0.9 4.4 3.3 1.0 4.3 28354091 1.0 1.0 1.0 2.5 1.7 1.0 0.9 2836 4072 1.0 1.0 2.1 1.0 5.9 2.0 5.12837 4022 3.5 4.5 0.8 1.0 3.0 1.0 3.2 2838 3965 1.9 5.6 0.4 1.0 5.5 2.34.1 2839 3954 1.0 2.7 1.3 3.6 2.8 1.9 2.6 2840 3872 1.0 3.2 1.3 2.8 4.01.8 3.9 2841 3869 1.0 1.0 5.8 3.8 1.0 0.7 0.6 2842 3838 1.0 1.6 1.2 2.02.6 1.7 1.9 2843 3806 0.6 2.6 0.9 3.7 3.0 1.0 3.4 2844 3798 10.2 0.9 2.90.3 0.7 1.0 0.4 2845 3792 1.0 1.0 1.0 2.7 2.9 1.0 2.5 2846 3788 1.7 5.41.2 3.4 2.5 1.3 2.7 2847 3767 1.1 2.2 0.7 1.7 2.5 1.0 2.5 2848 3458 1.23.3 0.7 2.0 2.6 1.0 2.2 2849 3251 0.4 0.5 1.4 2.7 1.4 1.0 1.0 2850 31941.0 2.3 1.3 3.1 2.2 1.3 3.2 2851 3102 0.5 3.2 1.0 4.8 2.9 1.0 2.3 28523094 11.5 0.8 2.7 0.3 0.6 1.0 0.4 2853 2671 0.8 1.6 1.0 2.2 2.8 1.9 1.02854 2634 0.9 2.8 0.4 1.0 3.8 1.7 4.0 2855 2567 4.6 3.3 0.8 0.6 2.6 1.03.3 2856 2317 1.0 1.0 2.4 1.0 1.0 1.0 1.1 2857 1958 0.3 0.6 1.0 2.6 0.90.8 0.9 2858 1680 0.3 4.7 1.0 17.7 2.7 1.0 4.5 2859 1625 2.2 7.8 0.5 1.83.1 1.7 3.4 2860 1445 0.2 0.6 1.0 2.7 0.8 0.9 0.9 2861 1320 4.9 1.0 2.40.4 0.6 1.2 0.5 2862 974 0.6 3.1 1.1 3.2 2.4 1.4 3.7 2863 726 1.0 1.01.0 1.0 1.0 1.0 1.0 2864 718 0.4 2.6 0.5 2.7 1.6 1.0 1.0 2865 703 1.04.1 1.0 2.4 1.6 1.0 1.7 2866 652 2.8 4.4 1.6 2.3 1.0 1.6 1.0 2867 6306.9 1.0 2.2 0.3 0.6 1.0 0.5 2868 593 1.0 4.3 1.0 2.3 1.0 1.0 1.0 2869532 1.3 4.7 1.0 2.4 2.6 2.2 4.0 2870 272 0.7 2.7 0.9 3.1 2.4 1.3 4.32871 256 0.6 3.2 0.5 1.9 2.8 1.0 3.4 2872 57 0.5 1.4 1.0 2.3 0.9 1.0 0.7

TABLE 20 SEQ ID NO SPOT ID 2506 10594 2507 21851 2508 20990 2509 186412510 19037 2511 398 2512 18773 2513 3583 2514 3418 2515 145306 2516 34182517 3418 2518 18985 2519 17229 2520 25930 2521 25930 2522 20701 252320346 2524 20346 2525 21247 2526 21247 2527 23062 2528 25666 2529 256662530 19001 2531 10897 2532 10897 2533 10897 2534 1960 2535 146262 253626381 2537 26381 2538 26719 2539 26719 2540 27152 2541 10926 2542 289802543 1236 2544 29350 2545 29350 2546 26242 2547 4098 2548 145253 25494098 2550 17432 2551 17432 2552 1785 2553 1785 2554 1785 2555 28856 255628856 2557 18791 2558 18791 2559 22950 2560 22950 2561 1882 2562 238862563 24995 2564 24995 2565 24477 2566 21681 2567 21681 2568 9557 25699557 2570 22033 2571 873 2572 17144 2573 26970 2574 26970 2575 214022576 27074 2577 27074 2578 10963 2579 10963 2580 29525 2581 29525 258225514 2583 25514 2584 26612 2585 26612 2586 24600 2587 9741 2588 97412589 9741 2590 23689 2591 23689 2592 22352 2593 23806 2594 12285 259527638 2596 27638 2597 9663 2598 9663 2599 26850 2600 10204 2601 102042602 10204 2603 25922 2604 25922 2605 26347 2606 26347 2607 20361 260820361 2609 28672 2610 28672 2611 25520 2612 25520 2613 1723 2614 17232615 28863 2616 25526 2617 25526 2618 27936 2619 27936 2620 26851 262125107 2622 25107 2623 25107 2624 24912 2625 24912 2626 25169 2627 256002628 25600 2629 28706 2630 28706 2631 26377 2632 26377 2633 19460 263425243 2635 20018 2636 20018 2637 918 2638 25027 2639 29089 2640 290892641 9141 2642 9141 2643 9141 2644 12005 2645 12148 2646 12148 264717394 2648 27017 2649 27017 2650 25809 2651 8719 2652 8719 2653 210302654 21030 2655 11436 2656 11436 2657 10374 2658 10374 2659 25861 266025861 2661 3317 2662 3317 2663 8743 2664 26240 2665 26240 2666 285622667 16877 2668 25955 2669 26308 2670 26308 2671 4140 2672 3436 267325612 2674 25612 2675 12257 2676 12257 2677 9111 2678 9111 2679 176202680 26025 2681 26025 2682 19271 2683 4151 2684 4151 2685 26569 268626569 2687 10344 2688 10344 2689 10344 2690 832 2691 832 2692 12071 269312071 2694 12271 2695 11433 2696 20917 2697 25810 2698 12039 2699 120392700 25499 2701 25499 2702 25557 2703 25557 2704 9917 2705 19505 270617491 2707 10683 2708 10683 2709 1936 2710 828 2711 9558 2712 9558 271320164 2714 969 2715 969 2716 9910 2717 2427 2718 19990 2719 20605 272020605 2721 10650 2722 10650 2723 25963 2724 25963 2725 25562 2726 255622727 3429 2728 2725 2729 19923 2730 20457 2731 20457 2732 24773 273324119 2734 3908 2735 3908 2736 8560 2737 8560 2738 9377 2739 9377 274017618 2741 12136 2742 17373 2743 18577 2744 18577 2745 3143 2746 177372747 17737 2748 20029 2749 20029 2750 18537 2751 18537 2752 12102 275312102 2754 8487 2755 9252 2756 9252 2757 25605 2758 25605 2759 296522760 10858 2761 1261 2762 4156 2763 4156 2764 3452 2765 3452 2766 27482767 2046 2768 2046 2769 2044 2770 2044 2771 1342 2772 1342 2773 13262774 1326 2775 9981 2776 9981 2777 27917 2778 8488 2779 22793 2780 227932781 26883 2782 26883 2783 11540 2784 17707 2785 20649 2786 20649 278724004 2788 24004 2789 11836 2790 11836 2791 11836 2792 24932 2793 191432794 19143 2795 26257 2796 26257 2797 21239 2798 21239 2799 16959 28002568 2801 25936 2802 25936 2803 23041 2804 9206 2805 25105 2806 251052807 24779 2808 22451 2809 22451 2810 22291 2811 22291 2812 21143 281324751 2814 24751 2815 24294 2816 24294 2817 24006 2818 24006 2819 256782820 25678 2821 22027 2822 29495 2823 29495 2824 24577 2825 24577 282624577 2827 23527 2828 17090 2829 25137 2830 23772 2831 1659 2832 84972833 25272 2834 21216 2835 21216 2836 21216 2837 11939 2838 11939 283911939 2840 9191 2841 3429 2842 24588 2843 4047 2844 28344 2845 283442846 27561 2847 3272 2848 26735 2849 26735 2850 24900 2851 24900 28529472 2853 9472 2854 9979 2855 21996 2856 22312 2857 11327 2858 182402859 18240 2860 21922 2861 21922 2862 22290 2863 10390 2864 10390 28652212 2866 20213 2867 20213 2868 24955 2869 19574 2870 19969 2871 85702872 18519 2506 9616 2507 9616 2508 17459 2509 17459 2510 25193 251125193 2512 25193 2513 25191 2514 22566 2515 4164 2516 4146 2517 40722518 4022 2519 3954 2520 3838 2521 3806 2522 3798 2523 3792 2524 37882525 3458 2526 3194 2527 3102 2528 25191 2529 25191 2530 9448 2531 94482532 25224 2533 20218 2534 3089 2535 3089 2536 19953 2537 19953 253822362 2539 25516 2540 25516 2541 25757 2542 24814 2543 21994 2544 271172545 22745 2546 24233 2547 2001 2548 2001 2549 2001 2550 17147 255121214 2552 21214 2553 21214 2554 26422 2555 21965 2556 25541 2557 255412558 18302 2559 18302 2560 24049 2561 24049 2562 26326 2563 26326 25642254 2565 162502 2566 10296 2567 20044 2568 28806 2569 17566 2570 175662571 19005 2572 3567 2573 159223 2574 3567 2575 3567 2576 458 2577 214112578 22972 2579 24853 2580 21502 2581 18180 2582 23918 2583 24144 258419996 2585 11528 2586 20506 2587 20506 2588 23833 2589 20042 2590 200422591 11646 2592 10577 2593 10577 2594 18556 2595 29433 2596 28763 259727450 2598 27450 2599 27255 2600 26550 2601 26550 2602 26508 2603 263342604 26334 2605 26027 2606 26027 2607 25977 2608 25977 2609 25965 261025965 2611 25844 2612 25844 2613 25834 2614 25816 2615 25746 2616 257122617 25621 2618 25621 2619 25614 2620 25614 2621 25603 2622 25603 262325556 2624 25556 2625 25555 2626 25555 2627 3094 2628 2567 2629 19582630 1680 2631 1445 2632 1320 2633 974 2634 652 2635 630 2636 593 2637256

Example 41 Cyclin g Associated Kinase (GAK)

A gene or product thereof called cyclin G associated kinase, or GAK, wasidentified as being overexpressed in 3D T4-2 cultures relative to both3D S1 cultures (ratio: 7.9296) and 2D T4-2 cultures (ratio: 34.6682)(Sample ID RG:1056692:10012:C11, Spot ID 19990). GAK corresponds toGenbank Accession number XM_(—)003450.

Example 42 Antisense Regulation of GAK Expression

Additional functional information on GAK was generated using antisenseknockout technology. A number of different oligonucleotidescomplementary to GAK mRNA were designed (AS) with corresponding controls(RC): GGAATCACCGCTTTGCCATCTTCAA (SEQ ID NO:3005; CHIR159-1AS,gak:P1868AS), AACTTCTACCGTTTCGCCACTAAGG (SEQ ID NO:3006; CHIR159-1RC,gak:P1868RC); GACCGTGTACTGCGTGTCGTGCG (SEQ ID NO:3007; CHIR159-7AS,gak:P0839AS) and GCGTGCTGTGCGTCATGTGCCAG (SEQ ID NO: 3008; CHIR159-7RC,gak:P0839RC), and tested for their ability to suppress expression of GAKin human malignant colorectal carcinoma SW620 cells, human breast cancerMDA231 cells, and human breast cancer T4-2 cells. For each transfectionmixture, a carrier molecule, preferably a lipitoid or cholesteroid, wasprepared to a working concentration of 0.5 mM in water, sonicated toyield a uniform solution, and filtered through a 0.45 μm PVDF membrane.The antisense or control oligonucleotide was then prepared to a workingconcentration of 100 μM in sterile Millipore water. The oligonucleotidewas further diluted in OptiMEM™ (Gibco/BRL), in a microfuge tube, to 2μM, or approximately 20 μg oligo/ml of OptiMEM™. In a separate microfugetube, lipitoid or cholesteroid, typically in the amount of about 1.5-2nmol lipitoid/μg antisense oligonucleotide, was diluted into the samevolume of OptiMEM™ used to dilute the oligonucleotide. The dilutedantisense oligonucleotide was immediately added to the diluted lipitoidand mixed by pipetting up and down. Oligonucleotide was added to thecells to a final concentration of 300 nM.

The level of target mRNA (GAK) in the transfected cells was quantitatedin the cancer cell lines using the methods using primers CHIR159_(—)2896(GCCGTCTTCAGGCAACAACTCCCA; SEQ ID NO: 3009; forward) and CHIR159_(—)3089(TGCTGGACGAGGCTGTCATCTTGC; SEQ ID NO: 3010; reverse). RNA was extractedas above according to manufacturer's directions.

Quantitative PCR (qPCR) was performed by first isolating the RNA fromthe above mentioned tissue/cells using a Qiagen RNeasy mini prep kit. Atotal of 0.5 micrograms of RNA was used to generate a first strand cDNAusing Stratagene MuLV Reverse Transcriptase, using recommendedconcentrations of buffer, enzyme, and Rnasin. Concentrations and volumesof dNTP, and oligo dT, or random hexamers were lower than recommended toreduce the level of background primer dimerization in the qPCR.

The cDNA is then used for qPCR to determine the levels of expression ofGAK using the GeneAmp 7000 by ABI as recommended by the manufacturer.Primers for actin were also used in order to normalized the values, andeliminate possible variations in cDNA template concentrations, pipettingerror, etc.

For each 20 μl reaction, extracted RNA (generally 0.2-1 μg total) wasplaced into a sterile 0.5 or 1.5 ml microcentrifuge tube, and water wasadded to a total volume of 12.5 μl. To each tube was added 7.5 μl of abuffer/enzyme mixture, prepared by mixing (in the order listed) 2.5 μlH₂O, 2.0 μl 10× reaction buffer, 10 μl oligo dT (20 μmol), 1.0 μl dNTPmix (10 mM each), 0.5 μl RNAsin® (20 u) (Ambion, Inc., Hialeah, Fla.),and 0.5 μl MMLV reverse transcriptase (50 u) (Ambion, Inc.). Thecontents were mixed by pipetting up and down, and the reaction mixturewas incubated at 42° C. for 1 hour. The contents of each tube werecentrifuged prior to amplification.

An amplification mixture was prepared by mixing in the following order:1×PCR buffer II, 3 mM MgCl₂, 140 μM each dNTP, 0.175 μmol each oligo,1:50,000 dil of SYBR® Green, 0.25 mg/ml BSA, 1 unit Taq polymerase, andH₂O to 20 μl. (PCR buffer II is available in 10× concentration fromPerkin-Elmer, Norwalk, Conn.). In 1× concentration it contains 10 mMTris pH 8.3 and 50 mM KCl. SYBR® Green (Molecular Probes, Eugene, Oreg.)is a dye which fluoresces when bound to double stranded DNA. As doublestranded PCR product is produced during amplification, the fluorescencefrom SYBR® Green increases. To each 20 μl aliquot of amplificationmixture, 2 μl of template RT was added, and amplification was carriedout according to standard protocols.

Table 21 shows that the antisense oligonucleotides described abovereduced expression of GAK mRNA as compared to controls in all three celllines. GAK mRNA reduction ranged from about 50% to about 90%, ascompared to cells transfected with reverse (i.e. sense) controloligonucleotides.

TABLE 21 antisense regulation of GAK mRNA Gene Actin Percent Oligo CellLine Message Message Ratio KO CHIR159-1AS SW620 0.0923 0.669 0.138 90.7CHIR159-1RC SW620 1.01 0.680 1.49 CHIR159-7AS SW620 0.0555 0.678 0.08285.4 CHIR159-7RC SW620 0.335 0.598 0.560 CHIR159-1AS MDA231 0.358 0.6870.521 59.3 CHIR159-1RC MDA231 1.00 0.784 1.28 CHIR159-7AS MDA231 0.2620.674 0.389 69.4 CHIR159-7RC MDA231 0.840 0.659 1.27 CHIR159-1AS T4-20.307 0.707 0.434 72.9 CHIR159-1RC T4-2 1.23 0.770 1.60 CHIR159-7AS T4-20.214 0.649 0.330 49.8 CHIR159-7RC T4-2 0.506 0.770 0.657

Reduction of GAK protein by antisense polynucleotides in SW620, MDA231and T4-2 was confirmed using an antibody that specifically recognizesGAK. FIG. 38 shows a western (i.e. protein) blot of protein extracts ofthe above cell lines decorated with anti-GAK antibodies. GAK proteinexpression is reduced in cell lines receiving GAK antisenseoligonucleotides.

Example 43 Role of GAK in Anchorage Independent Cell Growth

The effect of GAK gene expression upon anchorage-independent cell growthof SW620 and MBA-231 cells was measured by colony formation in softagar. Soft agar assays were performed by first coating a non-tissueculture treated plate with PolyHEMA to prevent cells from attaching tothe plate. Non-transfected cells were harvested using 0.05% trypsin andwashing twice in media. The cells are counted using a hemacytometer andresuspended to 10⁴ per ml in media. 50 μl aliquots are placed inpoly-HEMA coated 96-well plates and transfected. For each transfectionmixture, a carrier molecule, preferably a lipitoid or cholesteroid, wasprepared to a working concentration of 0.5 mM in water, sonicated toyield a uniform solution, and filtered through a 0.45 μm PVDF membrane.The antisense or control oligonucleotide was then prepared to a workingconcentration of 100 μM in sterile Millipore water. The oligonucleotidewas further diluted in OptiMEM™ (Gibco/BRL), in a microfuge tube, to 2μM, or approximately 20 μg oligo/ml of OptiMEM™. In a separate microfugetube, lipitoid or cholesteroid, typically in the amount of about 1.5-2nmol lipitoid/μg antisense oligonucleotide, was diluted into the samevolume of OptiMEM™ used to dilute the oligonucleotide. The dilutedantisense oligonucleotide was immediately added to the diluted lipitoidand mixed by pipetting up and down. Oligonucleotide was added to thecells to a final concentration of 300 nM. Following transfection (˜30minutes), 3% GTG agarose is added to the cells for a final concentrationof 0.35% agarose. After the cell layer agar solidifies, 100 μl of mediais dribbled on top of each well. Colonies form in 7 days. For a read-outof growth, 20 μl of Alamar Blue is added to each well and the plate isshaken for 15 minutes. Fluorecence readings (530 nm excitation 590 nmemission) are taken after incubation for 6-24 hours.

The data presented in Table 22 shows that the application of GAKantisense oligonucleotides to SW620 and MDA 231 cells results ininhibition of colony formation and shows that GAK plays a role inproduction anchorage-independent cell growth. Table 22 shows the averagefluorescence reading for several experiments. The standard deviation(St. Dev) of the fluorescence reading and coefficient of variation (%CV) is also shown.

TABLE 22 GAK and anchorage-independent cell growth. Oligo Cell LineAverage St. Dev % CV Blank SW620 12868.17 208.78 1.78 Untreated SW62031075.17 1944.36 7.66 Pos Control SW620 5717.17 1108.71 23.75 NegControl SW620 7576.17 465.95 7.63 Chir159-1AS SW620 9701.5 2281.36 28.8Chir159-1RC SW620 17765.5 1958.45 13.5 Blank MDA231 12726.83 232.45 2Untreated MDA231 87272.17 0 0 Pos Control MDA231 10645.17 1591.08 18.31Neg Control MDA231 24159.5 2850.58 14.45 Chir159-1AS MDA231 8613.54852.76 69 Chir159-1RC MDA231 17859.17 1535.55 10.53

Example 44 DKFZP566I133 (DKFZ)

Several previously uncharacterized genes were identified as beinginduced in these experiments. One such gene was represented by twospots, Spot ID Nos 22793 and 26883 (gene assignment DKFZp566I133). Thisgene was expressed at a ratio of about 2.2 in two 2-dimensional (2D)T4-2 vs. 2D S1 experiments, and also at a ratio of about 2 when3-dimensional (3D) T4-2 cells were compared to the various tumorreversion cultures. However, the ratio of expression increased to anaverage of 3.2 when 3-dimensional (3D) T4-2 cultures were compared to 2DS1 cultures. In contrast, there was essentially no difference inexpression levels when 3D S1 cultures were compared to 2D S1 cultures,suggesting that expression of this gene is specifically elevated in thetumorigenic cell line T4-2, and even further elevated when thetumorigenic cell line is grown in three dimensional cultures (see Table23).

TABLE 23 Spot 2D T4-2/ 3D T42/ 3D S1/ 3D T4-2/ 3D T4-2/ 3D T4-2/B1 3DT4-2/ ID 2D S1 3D S1 2D S1 2D T4-2 EGFRAb integrin Ab Tyr 22893 1.903872.64711 0.522161 1 2.17956 1.75287 2.055538 26883 2.43428 3.746130.524466 1 2.467573 2.029468 2.002817

These array data were confirmed by qPCR using the methods describedabove and the gene specific PCR primersCHIR180_(—)1207ACAGGGAGAAAACTGGTTGTCCTGG (SEQ ID NO:3011; Forward) andCHIR180_(—)1403 AAGGCAGAACCCATCCACTCCAA (SEQ ID NO:3012; Reverse).Independent cultures were used for these experiments, and data wasnormalized to B-catenin. These data are shown in Table 24

TABLE 24 3D B1 3D Integrin 2D S1 2D T4-2 S1 3D T4-2 3D EGFRAb Ab 3D Tyr0.165 0.421 0.14 0.475 0.231 0.175 0.174

DKFZ corresponds to Genbank Accession numbers NP_(—)112200, AAH09758,and NM_(—)030938. Orthologs of DKFZ are identified in species other thanHomo sapiens include NM_(—)138839 from Rattus norvegicus.

Analysis of the sequence of DKFZ using a transmembrane helix predictionalgorithm (Sonhammer, et al, A hidden Markov model for predictingtransmembrane helices in protein sequences, In Proc. of Sixth Int. Conf.on Intelligent Systems for Molecular Biology, p. 175-82, Ed. J. Glasgow,T. Littlejohn, F. Major, R. Lathrop, D. Sankoff, and C. Sensen, MenloPark, Calif.: AAAI Press, 1998) indicates that the DKFZ protein has sixtransmembrane regions (FIG. 18), and, as such, is likely to be atransmembrane protein.

Example 45 Antisense Regulation of DKFZ Expression

Additional functional information on DKFZ was generated using antisenseknockout technology. A number of different oligonucleotidescomplementary to DKFZ mRNA were designed (AS) with correspondingcontrols (RC): GCTGCTGGATTCGTTTGGCATAACT (SEQ ID NO: 3013; CHIR180-7AS,DKFZp56611:P1301AS), TCAATACGGTTTGCTTAGGTCGTCG (SEQ ID NO: 3014;CHIR180-7RC, DKFZp56611:P1301RC), TCTCCTCTGAGTTCAACCGCTGCT (SEQ ID NO:3015; CHIR180-8AS, DKFZp56611:P1320AS) and TCGTCGCCAACTTGAGTCTCCTCT (SEQID NO: 3016; CHIR180-8RC, DKFZp56611:P1320AS), and tested for theirability to suppress expression of DKFZ in human malignant colorectalcarcinoma SW620 cells, human breast cancer MDA231 cells, and humanbreast cancer T4-2 cells, as described above.

Table 25 shows that the antisense (AS) oligonucleotides described abovereduced expression of DKFZ mRNA as compared to controls in all threecell lines. DKFZ mRNA reduction ranged from about 95% to about 99%, ascompared to cells transfected with reverse (i.e. sense) control (RC)oligonucleotides.

TABLE 25 antisense regulation of DKFZ mRNA Gene Actin Percent Oligo CellLine Message Message Ratio KO CHIR180-7AS SW620 0.0157 0.772 0.020 99.3CHIR180-7RC SW620 1.99 0.736 2.70 CHIR180-8AS SW620 0.0387 0.681 0.05797.9 CHIR180-8RC SW620 1.89 0.703 2.69 CHIR180-7AS MDA231 0.0471 3.580.013 98.5 CHIR180-7RC MDA231 1.99 2.33 0.854 CHIR180-8AS MDA231 0.009351.74 0.00537 99.5 CHIR180-8RC MDA231 1.14 1.01 1.13 CHIR180-7AS T4-20.119 0.667 0.178 95.4 CHIR180-7RC T4-2 2.8 0.728 3.85 CHIR180-8AS T4-20.0852 0.751 0.113 95.6 CHIR180-8RC T4-2 1.6 0.620 2.58

Example 46 Effect of DKFZ Expression on Cell Proliferation

The effect of gene expression on the inhibition of cell proliferationwas assessed in metastatic breast cancer cell line MDA-231 and breastcancer cell line T4-2.

Cells were plated to approximately 60-80% confluency in 96-well dishes.Antisense or reverse control oligonucleotide was diluted to 2 μM inOptiMEM™ and added to OptiMEM™ into which a delivery vehicle, preferablya lipitoid or cholesteroid, had been diluted. The oligo/delivery vehiclemixture was then further diluted into medium with serum on the cells.The final concentration of oligonucleotide for all experiments was 300nM, and the final ratio of oligo to delivery vehicle for all experimentswas 1.5 nmol lipitoid/μl oligonucleotide.

Antisense oligonucleotides were prepared. Cells were transfected for 4hours or overnight at 37° C. and the transfection mixture was replacedwith fresh medium. Plates are incubated for 4 days, with a plateharvested for each day0-day4. To determine differences in cell number, aCyQuant Cell Proliferation Assay kit (Molecular Probes) was used permanufacturer's instructions. Fluorecence readings (480 nm excitation 520nm emission) are taken after incubation for 5 minutes.

The results of these assays are shown in Tables 26 and 27. The data showthat DKFZ antisense polynucleotides significantly reduce cellproliferation as compared to controls, and, as such, DKFZ plays a rolein production or maintenance of the cancerous phenotype in cancerousbreast cells.

TABLE 26 Cell proliferation Ave Day Ave Ave Av3 Ave Oligo Cell Line 0Day 1 Day 2 Day 3 Day 4 Untreated MDA231 4233 4858 9544 10981 16776Untreated MDA231 3849 4036 8686 9855 14865 Pos Control MDA231 3630 22363564 4536 7477 Neg Control MDA231 4913 5127 8331 8887 13620 CHIR180-7ASMDA231 3848 3476 6942 8715 11925 CHIR180-7RC MDA231 4895 4700 8484 1031814226 Untreated T4-2 4062 3389 5438 10579 15617 Untreated T4-2 4209 38026346 11802 16275 Pos Control T4-2 3985 2712 4081 6404 9685 Neg ControlT4-2 4051 3901 4356 9425 12964 CHIR180-7AS T4-2 3792 3201 3849 737610911 CHIR180-7RC T4-2 3967 3840 4321 8382 12293

TABLE 27 Standard Deviations P-Value of T-Test Oligo Day 0 Day 1 Day 2Day 3 Day 4 Day 0 Day 1 Day 2 Day 3 Day 4 Untreated 337 269 299 697 13330.1306 0.1063 0.1804 0.0926 0.1225 Untreated 99 631 867 547 1047 0.13060.1063 0.1804 0.0926 0.1225 Pos 94 118 89 441 974 0.0000 0.0001 0.00030.0001 0.0010 Control Neg 2 252 697 195 780 0.0000 0.0001 0.0003 0.00010.0010 Control CHIR180-7AS 292 16 435 398 418 0.0072 0.0276 0.00590.0140 0.0028 CHIR180-7RC 208 6 244 533 440 0.0072 0.0276 0.0059 0.01400.0028 Untreated 64 283 789 1593 1226 0.2550 0.0921 0.1257 0.2794 0.4352Untreated 22 158 205 577 478 0.2550 0.0921 0.1257 0.2794 0.4352 Pos 122213 6 475 957 0.4320 0.0065 0.2624 0.0051 0.0293 Control Neg 47 335 464809 1417 0.4320 0.0065 0.2624 0.0051 0.0293 Control CHIR180-7AS 170 679263 127 1330 0.2638 0.0976 0.3516 0.0040 0.0039 CHIR180-7RC 22 453 646579 884 0.2638 0.0976 0.3516 0.0040 0.0039

Example 47 Role of DKFZ in Anchorage Independent Cell Growth

The effect of DKFZ gene expression upon anchorage-independent cellgrowth of MDA435 and MCF7 human breast cancer cells was measured bycolony formation in soft agar. Soft agar assays were conducted by themethod described for GAK, above.

The data presented in Table 28 shows that the application of DKFZantisense oligonucleotides to MDA435 and MCF7 cells results ininhibition of colony formation and shows that DKFZ plays a role inanchorage-independent cell growth of cancer cells. Table 28 shows theaverage fluorescence reading for several experiments. The standarddeviation (St. Dev) of the fluorescence reading and coefficient ofvariation (% CV) and probability (P-value) is also shown.

TABLE 28 Oligo Cell Line Average St. Dev % CV P-Value Untreated MDA43531190 5838 19 0.1342 Untreated MDA435 38623 3620 9 0.1342 Pos ControlMDA435 4776 818 17 0.0156 Neg Control MDA435 16315 481 3 0.0156Chir180-7AS MDA435 21161 3439 16 0.0274 Chir180-7RC MDA435 28868 1902 70.0274 Untreated MCF7 18954 1478 8 0.1476 Untreated MCF7 14383 4163 290.1476 Pos Control MCF7 1036 194 19 0.0036 Neg Control MCF7 9478 2382 250.0036 Chir180-7AS MCF7 4752 2002 42 0.0139 Chir180-7RC MCF7 9570 18 00.0139

The effect of DKFZ gene expression upon invasiveness of MDA231 humanbreast cancer cells was measured by a matrigel assay. A 3-dimensionalreconstituted basement membrane culture of cells was generated asdescribed previously (Peterson et al., (1992) Proc. Natl. Acad. Sci. USA89:9064-9068) using a commercially prepared reconstituted basementmembrane (Matrigel; Collaborative Research, Waltham, Mass.) and examinedusing methods well known in the art.

Table 29 (quantitated using Alamar Blue similar to the soft agar assay)and FIG. 40 provides exemplary results of the Matrigel invasion/motilityassay to test the invasiveness of MDA231 cells with reduced expressionof DKFZ. In general, these data show that a reduction in the expressionof DKFZ significantly decreases the invasiveness of MDA231 cells.

TABLE 29 Oligo Cell Line Average St. Dev % CV P-Value Untreated MDA23128316 13663 48 0.9080 Untreated MDA231 26840 15669 58 0.9080 Pos ControlMDA231 2756 487 18 0.0002 Neg Control MDA231 14301 1386 10 0.0002Chir180-7AS MDA231 10508 1963 19 0.0287 Chir180-7RC MDA231 14310 153 10.0287

Example 48 Expression of DKFZ in Cancer Tissues

The following peptides were used for polyclonal antibody production:peptide 809: gvhqqyvqriek (SEQ ID NO:2885), corresponding to amino acids97-108 of the DKFZ protein and peptide 810: sgaepddeeyqef (SEQ ID NO:2886), corresponding to amino acids 215-227 of the DKFZ protein.

Antibodies specific for DKFZ are used in FACS and immunolocalizationanalysis to show that DKFZ is associated with membrane, and up-regulatedin cancer tissues of biopsies from cancer patients.

Further, antibodies specific for DKFZ are used to modulate DKFZ activityin cancerous breast, and is further used, alone or conjugated to a toxicmoiety, as a treatment for breast cancer.

Example 49 Source of Biological Materials

The biological materials used in the experiments that led to the presentinvention are described below.

Source of Patient Tissue Samples

Normal and cancerous tissues were collected from patients using lasercapture microdissection (LCM) techniques, which techniques are wellknown in the art (see, e.g., Ohyama et al. (2000) Biotechniques29:530-6; Curran et al. (2000) Mol. Pathol. 53:64-8; Suarez-Quian et al.(1999) Biotechniques 26:328-35; Simone et al. (1998) Trends Genet.14:2726; Conia et al. (1997) J. Clin. Lab. Anal. 11:28-38; Emmert-Bucket al. (1996) Science 274:9981001). Table 30 provides information abouteach patient from which colon tissue samples were isolated, including:the Patient ID (“PT ID”) and Path ReportlD (“Path ID”), which arenumbers assigned to the patient and the pathology reports foridentification purposes; the group (“Grp”) to which the patients havebeen assigned; the anatomical location of the tumor (“Anatom Loc”); theprimary tumor size (“Size”); the primary tumor grade (“Grade”); theidentification of the histopathological grade (“Histo Grade”); adescription of local sites to which the tumor had invaded (“LocalInvasion”); the presence of lymph node metastases (“Lymph Met”); theincidence of lymph node metastases (provided as a number of lymph nodespositive for metastasis over the number of lymph nodes examined) (“LymphMet Incid”); the regional lymphnode grade (“Reg Lymph Grade”); theidentification or detection of metastases to sites distant to the tumorand their location (“Dist Met & Loc”); the grade of distant metastasis(“Dist Met Grade”); and general comments about the patient or the tumor(“Comments”). Histopathology of all primary tumors indicated the tumorwas adenocarcinoma except for Patient ID Nos. 130 (for which noinformation was provided), 392 (in which greater than 50% of the cellswere mucinous carcinoma), and 784 (adenosquamous carcinoma). Extranodalextensions were described in three patients, Patient ID Nos. 784, 789,and 791. Lymphovascular invasion was described in Patient ID Nos. 128,228, 278, 517, 534, 784, 786, 789, 791, 890, and 892. Crohn's-likeinfiltrates were described in seven patients, Patient ID Nos. 52, 264,268, 392, 393, 784, and 791.

TABLE 30 Path Anatom Histo Pt ID ID Grp Loc Size Grade Grade LocalInvasion  10 16 III Cecum 8.5 T3 G2 through muscularis propriaapproaching pericolic fat, but not at serosal surface  15 21 IIIAscending 4.0 T3 G2 Extending into colon subserosal adipose tissue  5271 II Cecum 9.0 T3 G3 Invasion through muscularis propria, subserosalinvolvement; ileocec. valve involvement 121 140 II Sigmoid 6 T4 G2Invasion of muscularis propria into serosa, involving submucosa ofurinary bladder 125 144 II Cecum 6 T3 G2 Invasion through the muscularispropria into suserosal adipose tissue. Ileocecal junction. 128 147 IIITransverse 5.0 T3 G2 Invasion of colon muscularis propria intopercolonic fat 130 149 Splenic 5.5 T3 through wall and flexure intosurrounding adipose tissue 133 152 II Rectum 5.0 T3 G2 Invasion throughmuscularis propria into non- peritonealized pericolic tissue; grossconfiguration is annular. 141 160 IV Cecum 5.5 T3 G2 Invasion ofmuscularis propria into pericolonic adipose tissue, but not throughserosa. Arising from tubular adenoma. 156 175 III Hepatic 3.8 T3 G2Invasion through flexure mucsularis propria into subserosa/pericolicadipose, no serosal involvement. Gross configuration annular. 228 247III Rectum 5.8 T3 G2 to Invasion through G3 muscularis propria toinvolve subserosal, perirectoal adipose, and serosa 264 283 II Ascending5.5 T3 G2 Invasion through colon muscularis propria into subserosaladipose tissue. 266 285 III Transverse 9 T3 G2 Invades through colonmuscularis propria to involve pericolonic adipose, extends to serosa.267 286 III Ileocecal 4.5 T2 G2 Confined to muscularis propria 268 287 ICecum 6.5 T2 G2 Invades full thickness of muscularis propria, butmesenteric adipose free of malignancy 278 297 III Rectum 4 T3 G2Invasion into perirectal adipose tissue. 295 314 II Ascending 5.0 T3 G2Invasion through colon muscularis propria into percolic adipose tissue.296 315 III Cecum 5.5 T3 G2 Invasion through muscularis propria andinvades pericolic adipose tissue. Ileocecal junction. 300 319 IIIDescending 5.2 T2 G2 through the colon muscularis propria into pericolicfat 322 341 II Sigmoid 7 T3 G2 through the muscularis propria intopericolic fat 339 358 II Rectosigmoid 6 T3 G2 Extends into perirectalfat but does not reach serosa 341 360 II Ascending 2 cm T3 G2 Invasionthrough colon invasive muscularis propria to involve pericolonic fat.Arising from villous adenoma. 356 375 II Sigmoid 6.5 T3 G2 Through colonwall into subserosal adipose tissue. No serosal spread seen. 360 412 IIIAscending 4.3 T3 G2 Invasion thru colon muscularis propria topericolonic fat 392 444 IV Ascending 2 T3 G2 Invasion through colonmuscularis propria into subserosal adipose tissue, not serosa. 393 445II Cecum 6.0 T3 G2 Cecum, invades through muscularis propria to involvesubserosal adipose tissue but not serosa. 413 465 IV Cecum 4.8 T3 G2Invasive through muscularis to involve periserosal fat; abuttingileocecal junction. 452 504 II Ascending 4 T3 G2 through colonmuscularis propria approaching pericolic fat, but not at serosal surface505 383 IV 7.5 T3 G2 Invasion through muscularis propria involvingpericolic adipose, serosal surface uninvolved 517 395 IV Sigmoid 3 T3 G2penetrates muscularis propria, involves pericolonic fat. 534 553 IIAscending 12 T3 G3 Invasion through colon the muscularis propriainvolving pericolic fat. Serosa free of tumor. 546 565 IV Ascending 5.5T3 G2 Invasion through colon muscularis propria extensively throughsubmucosal and extending to serosa. 577 596 II Cecum 11.5 T3 G2 Invasionthrough the bowel wall, into suberosal adipose. Serosal surface free oftumor. 695 714 II Cecum 14.0 T3 G2 extending through bowel wall intoserosal fat 784 803 IV Ascending 3.5 T3 G3 through colon muscularispropria into pericolic soft tissues 786 805 IV Descending 9.5 T3 G2through colon muscularis propria into pericolic fat, but not at serosalsurface 787 806 II Rectosigmoid 2.5 T3 G2-G3 Invasion of muscularispropria into soft tissue 789 808 IV Cecum 5.0 T3 G2-G3 Extending throughmuscularis propria into pericolonic fat 790 809 IV Rectum 6.8 T3 G1-G2Invading through muscularis propria into perirectal fat 791 810 IVAscending 5.8 T3 G3 Through the colon muscularis propria into pericolicfat 888 908 IV Ascending 2.0 T2 G1 Into muscularis colon propria 889 909IV Cecum 4.8 T3 G2 Through muscularis propria int subserosal tissue 890910 IV Ascending T3 G2 Through colon muscularis propria into subserosa.891 911 IV Rectum 5.2 T3 G2 Invasion through muscularis propria intoperirectal soft tissue 892 912 IV Sigmoid 5.0 T3 G2 Invasion intopericolic sort tissue. Tumor focally invading skeletal muscle attachedto colon. 893 913 IV Transverse 6.0 T3 G2-G3 Through colon muscularispropria into pericolic fat 989 1009 IV Sigmoid 6.0 T3 G2 Invasionthrough colon wall and focally involving subserosal tissue. Lymph RegDist Lymph Met Lymph Dist Met Met Pt ID Met Incid Grade & Loc GradeComment  10 Pos 1/17 N1 Neg M0 Moderately differentiated  15 Pos 3/8  N1Neg MX invasive adenocarcinoma, moderately differentiated; focalperineural invasion is seen  52 Neg 0/12 N0 Neg M0 Hyperplastic polyp inappendix. 121 Neg 0/34 N0 Neg M0 Perineural invasion; donut anastomosisNeg. One tubulovillous and one tubular adenoma with no high gradedysplasia. 125 Neg 0/19 N0 Neg M0 patient history of metastatic melanoma128 Pos 1/5  N1 Neg M0 130 Pos 10/24  N2 Neg M1 133 Neg 0/9  N0 Neg M0Small separate tubular adenoma (0.4 cm) 141 Pos 7/21 N2 Pos - M1Perineural Liver invasion identified adjacent to metastaticadenocarcinoma. 156 Pos 2/13 N1 Neg M0 Separate tubolovillous andtubular adenomas 228 Pos 1/8  N1 Neg MX Hyperplastic polyps 264 Neg 0/10N0 Neg M0 Tubulovillous adenoma with high grade dysplasia 266 Neg 0/15N1 Pos - MX Mesenteric deposit 267 Pos 2/12 N1 Neg M0 268 Neg 0/12 N0Neg M0 278 Pos 7/10 N2 Neg M0 Descending colon polyps, no HGD orcarcinoma identified.. 295 Neg 0/12 N0 Neg M0 Melanosis coli anddiverticular disease. 296 Pos 2/12 N1 Neg M0 Tubulovillous adenoma (2.0cm) with no high grade dysplasia. Neg. liver biopsy. 300 Pos 2/2  N1 NegM0 322 Neg 0/5  N0 Neg M0 vascular invasion is identified 339 Neg 0/6 N0 Neg M0 1 hyperplastic polyp identified 341 Neg 0/4  N0 Neg MX 356 Neg0/4  N0 Neg M0 360 Pos 1/5  N1 Neg M0 Two mucosal polyps 392 Pos 1/6  N1Pos - M1 Tumor arising Liver at prior ileocolic surgical anastomosis.393 Neg 0/21 N0 Neg M0 413 Neg 0/7  N0 Pos - M1 rediagnosis of Liveroophorectomy path to metastatic colon cancer. 452 Neg 0/39 N0 Neg M0 505Pos 2/17 N1 Pos - M1 Anatomical Liver location of primary not notated inreport. Evidence of chronic colitis. 517 Pos 6/6  N2 Neg M0 No mentionof distant met in report 534 Neg 0/8  N0 Neg M0 Omentum with fibrosisand fat necrosis. Small bowel with acute and chronic serositis, focalabscess and adhesions. 546 Pos 6/12 N2 Pos - M1 Liver 577 Neg 0/58 N0Neg M0 Appendix dilated and fibrotic, but not involved by tumor 695 Neg0/22 N0 Neg MX moderately differentiated adenocarcinoma with mucinousdiferentiation (% not stated), tubular adenoma and hyperplstic polypspresent, 784 Pos 5/17 N2 Pos - M1 invasive poorly Liver differentiatedadenosquamous carcinoma 786 Neg 0/12 N0 Pos - M1 moderately Liverdifferentiated invasive adenocarcinoma 787 Neg N0 Neg MX Peritumorallymphocytic response; 5 LN examined in pericolic fat, no metastatasesobserved. 789 Pos 5/10 N2 Pos - M1 Three fungating Liver lesionsexamined. 790 Pos 3/13 N1 Pos - M1 Liver 791 Pos 13/25  N2 Pos - M1poorly Liver differentiated invasive colonic adenocarcinoma 888 Pos 3/21N0 Pos - M1 well to Liver moderately differentiated adenocarcinomas;this patient has tumors of the ascending colon and the sigmoid colon 889Pos 1/4  N1 Pos - M1 moderately Liver differentiated adenocarcinoma 890Pos 11/15  N2 Pos - M1 Liver 891 Pos 4/15 N2 Pos - M1 Perineural Liverinvasion present. 892 Pos 1/28 N1 Pos - M1 Perineural Liver, leftinvasion and right present, lobe, extensive. omentum Patient with ahistory of colon cancer. 893 Pos 14/17  N2 Pos - M1 Perineural Liverinvasion focally present. Omentum mass, but resection with no tumoridentified. 989 Pos 1/7  N1 Pos - M1 Primary Liver adenocarcinomaarising from tubulovillous adenoma.

Source of Polynucleotides on Arrays

Polynucleotides for use on the arrays were obtained from both publiclyavailable sources and from cDNA libraries generated from selected celllines and patient tissues. Table 31 provides information about thepolynucleotides on the arrays including: (1) the “SEQ ID NO” assigned toeach sequence for use in the present specification; (2) the spotidentification number (“Spot ID”), an internal reference that serves asa unique identifier for the spot on the array; (3) the “Clone ID”assigned to the clone from which the sequence was isolated; and (4) the“MAClone ID” assigned to the clone from which the sequence was isolated.The sequences corresponding to the SEQ ID NOS are provided in theSequence Listing.

TABLE 31 SEQ ID NO Spot ID Clone ID MAClone ID 3022 18 M00026919B:A10MA40:F01 3023 20 M00026919B:E07 MA40:G01 3024 22 M00026919D:F04 MA40:H013025 54 M00026914D:G06 MA40:A01 3026 56 M00026950A:A09 MA40:D07 3027 67M00003820C:A09 MA244:B01 3028 73 M00001673A:G03 MA244:E01 3029 115M00007939A:A12 MA27:B07 3030 119 M00007939A:B11 MA27:D07 3031 127M00007939B:G03 MA27:H07 3032 166 M00007997D:G08 MA29:C01 3033 220M00026894C:E11 MA39:F07 3034 238 M00001391A:C05 MA15:G01 3035 294M00006818A:A06 MA240:C01 3036 393 M00023278A:F09 MA36:E01 3037 405M00023299A:G01 MA36:C07 3038 411 M00023301A:A11 MA36:F07 3039 453M00008050A:D12 MA30:C01 3040 460 M00022135A:C04 MA35:F01 3041 462M00022137A:A05 MA35:G01 3042 466 M00022176C:A07 MA35:A07 3043 471M00008077B:A08 MA30:D07 3044 477 M00008077C:D09 MA30:G07 3045 492M00022081C:E09 MA34:F01 3046 495 M00001662A:G06 MA24:H01 3047 504M00022102B:B11 MA34:D07 3048 506 M00022102B:E08 MA34:E07 3049 556M00022569D:G06 MA22:F01 3050 577 M00001358B:B11 MA14:A01 3051 578M00001429A:G04 MA16:A01 3052 579 M00001358B:F05 MA14:B01 3053 582M00001429C:C03 MA16:C01 3054 585 M00001359D:B04 MA14:E01 3055 587M00001360A:E10 MA14:F01 3056 589 M00001360C:B05 MA14:G01 3057 590M00001430B:F01 MA16:G01 3058 592 M00001430C:A02 MA16:H01 3059 594M00001445C:H05 MA16:A07 3060 596 M00001445D:D07 MA16:B07 3061 605M00001374D:D10 MA14:G07 3062 607 M00001375A:A08 MA14:H07 3063 643M00006600A:E07 MA241:B01 3064 661 M00006690A:F06 MA241:C07 3065 739M00023325D:A08 MA37:B02 3066 742 M00026921D:F12 MA40:C02 3067 743M00023325D:F06 MA37:D02 3068 750 M00026924A:E09 MA40:G02 3069 823M00007940C:A04 MA27:D08 3070 827 M00007941C:H03 MA27:F08 3071 828M00021638B:F03 MA31:F08 3072 831 M00007941D:C04 MA27:H08 3073 842M00004054D:D02 3074 857 M00001507A:A10 MA23:E08 3075 858 M00004198D:A013076 861 M00001528C:B08 MA23:G08 3077 868 M00008002C:A05 MA29:B03 3078880 M00008006C:H05 MA29:H03 3079 898 M00026850C:A01 MA39:A02 3080 908M00026853D:C07 MA39:F02 3081 920 M00026896A:C09 MA39:D08 3082 934M00001391B:D02 MA15:C02 3083 938 M00001391B:H05 MA15:E02 3084 940M00001391D:C07 MA15:F02 3085 942 M00001392B:B01 MA15:G02 3086 954M00001407B:C03 MA15:E08 3087 1011 M00005635B:E02 MA242:B08 3088 1017M00005636B:B06 MA242:E08 3089 1018 M00006971A:E06 MA240:E08 3090 1019M00005636D:B08 MA242:F08 3091 1107 M00023302C:A04 MA36:B08 3092 1117M00023305A:C02 MA36:G08 3093 1172 M00022180A:E08 MA35:B08 3094 1178M00022181C:H11 MA35:E08 3095 1193 M00001673A:C11 3096 1201M00003853B:C07 3097 1204 M00022106B:D04 MA34:B08 3098 1209M00003858B:G01 MA24:E08 3099 1214 M00022109B:A11 MA34:G08 3100 1260M00022921A:H05 MA22:F02 3101 1282 M00001430D:H07 MA16:A02 3102 1283M00001360D:H10 MA14:B02 3103 1284 M00001431A:E01 MA16:B02 3104 1285M00001361A:A02 MA14:C02 3105 1295 M00001362A:B03 MA14:H02 3106 1297M00001376C:C01 MA14:A08 3107 1300 M00001449A:D02 MA16:B08 3108 1301M00001378B:A02 MA14:C08 3109 1302 M00001450A:D12 MA16:C08 3110 1303M00001378C:D08 MA14:D08 3111 1310 M00001451D:F01 MA16:G08 3112 1349M00006628B:A02 MA241:C02 3113 1444 M00026926C:F03 MA40:B03 3114 1458M00026963B:H03 MA40:A09 3115 1464 M00026964A:E10 MA40:D09 3116 1468M00026965C:A11 MA40:F09 3117 1493 M00001398A:D11 MA244:C09 3118 1512M00008095C:H08 MA31:D03 3119 1523 M00007942A:F12 MA27:B09 3120 1554M00004212B:B12 MA25:A09 3121 1576 M00008014C:E11 MA29:D05 3122 1578M00008015A:B05 MA29:E05 3123 1586 M00022049A:B08 MA33:A05 3124 1602M00026856B:F08 MA39:A03 3125 1604 M00026856C:H12 MA39:B03 3126 1628M00026900D:A03 MA39:F09 3127 1630 M00026900D:C12 MA39:G09 3128 1632M00026901D:A03 MA39:H09 3129 1642 M00001393A:G03 MA15:E03 3130 1656M00001409B:D03 MA15:D09 3131 1658 M00001409B:G01 MA15:E09 3132 1660M00001410C:C09 MA15:F09 3133 1662 M00001410D:A03 MA15:G09 3134 1697M00005504D:F06 MA242:A03 3135 1709 M00005510D:H10 MA242:G03 3136 1726M00006990D:D06 MA240:G09 3137 1761 SL146 MA248:A03 3138 1775 SL153MA248:H03 3139 1785 SL198 MA248:E09 3140 1787 SL199 MA248:F09 3141 1789SL200 MA248:G09 3142 1797 M00023283D:C03 MA36:C03 3143 1799M00023283D:D03 MA36:D03 3144 1801 M00023284A:D09 MA36:E03 3145 1807M00023285D:C05 MA36:H03 3146 1809 M00023306C:H11 MA36:A09 3147 1813M00023308D:B06 MA36:C09 3148 1817 M00023309D:H04 MA36:E09 3149 1819M00023310A:D07 MA36:F09 3150 1875 M00008079C:H04 MA30:B09 3151 1883M00008080B:B10 MA30:F09 3152 1884 M00022198D:C02 MA35:F09 3153 1886M00022198D:G03 MA35:G09 3154 1895 M00003768B:B09 MA24:D03 3155 1910M00022110C:A08 MA34:C09 3156 1913 M00003886C:H08 MA24:E09 3157 1960M00023297B:A10 MA22:D03 3158 1966 M00023314C:G05 MA22:G03 3159 1991M00001363B:C04 MA14:D03 3160 1992 M00001434D:F08 MA16:D03 3161 1994M00001435B:A04 MA16:E03 3162 1996 M00001435B:B09 MA16:F03 3163 2000M00001435C:F08 MA16:H03 3164 2001 M00001381A:F03 MA14:A09 3165 2004M00001453B:E11 MA16:B09 3166 2008 M00001453C:D02 MA16:D09 3167 2050M00007121D:A05 MA243:A03 3168 2052 M00007122C:F03 MA243:B03 3169 2053M00006638A:G02 MA241:C03 3170 2059 M00006639B:H09 MA241:F03 3171 2064M00007127C:C11 MA243:H03 3172 2073 M00006720D:C11 MA241:E09 3173 2075M00006728C:E07 MA241:F09 3174 2156 M00026931D:E08 MA40:F04 3175 2158M00026932D:B08 MA40:G04 3176 2168 M00026969D:D02 MA40:D10 3177 2169M00023393B:E02 MA37:E10 3178 2185 M00003782D:D06 MA244:E04 3179 2189M00004105D:B04 MA244:G04 3180 2199 M00001556D:B11 MA244:D10 3181 2234M00021664B:G03 MA31:E10 3182 2242 M00004078A:A07 3183 2263M00001561A:B03 MA23:D10 3184 2284 M00008023C:A06 MA29:F07 3185 2286M00008024C:F02 MA29:G07 3186 2288 M00008024C:G06 MA29:H07 3187 2292M00022057C:H10 MA33:B07 3188 2294 M00022059B:B06 MA33:C07 3189 2324M00026902B:F10 MA39:B10 3190 2342 M00001394D:B08 MA15:C04 3191 2354M00001415A:G05 MA15:A10 3192 2356 M00001416B:E03 MA15:B10 3193 2368M00001421B:B12 MA15:H10 3194 2413 M00005528C:E02 MA242:G04 3195 2513M00023312D:F10 MA36:A10 3196 2566 M00022157A:C06 MA35:C04 3197 2576M00022165A:A11 MA35:H04 3198 2584 M00022206A:B10 MA35:D10 3199 2601M00003811B:F09 3200 2605 M00003812D:A11 3201 2606 M00022088D:C10MA34:G04 3202 2613 M00003910B:C12 3203 2689 M00001366A:F06 MA14:A04 32042692 M00001435C:F12 MA16:B04 3205 2694 M00001436B:E11 MA16:C04 3206 2695M00001366B:E01 MA14:D04 3207 2696 M00001436C:C03 MA16:D04 3208 2700M00001437A:B01 MA16:F04 3209 2702 M00001437B:B08 MA16:G04 3210 2712M00001467B:H05 3211 2716 M00001468A:D02 MA16:F10 3212 2756M00007131B:B11 MA243:B04 3213 2761 M00006650A:A10 MA241:E04 3214 2765M00006653C:B09 MA241:G04 3215 2766 M00007154B:H08 MA243:G04 3216 2769M00006740A:E02 MA241:A10 3217 2770 M00021621A:D04 MA243:A10 3218 2771M00006740B:F11 MA241:B10 3219 2773 M00006741C:A01 MA241:C10 3220 2780M00022171C:A04 MA243:F10 3221 2858 M00026937C:B08 MA40:E05 3222 2861M00023367A:H06 MA37:G05 3223 2876 M00026985C:E12 MA40:F11 3224 2916M00008100A:A07 MA31:B05 3225 2921 M00007936B:H07 MA27:E05 3226 2924M00008100C:E05 MA31:F05 3227 2937 M00007947B:B02 MA27:E11 3228 2956M00004105A:C09 MA25:F05 3229 2957 M00001433C:D09 MA23:G05 3230 2980M00008027B:D09 MA29:B09 3231 2984 M00008028D:B01 MA29:D09 3232 2988M00008039A:C09 MA29:F09 3233 3026 M00026905A:A10 MA39:A11 3234 3030M00026905D:C05 MA39:C11 3235 3054 M00001401B:A06 MA15:G05 3236 3056M00001402A:A08 MA15:H05 3237 3105 M00005534C:E12 MA242:A05 3238 3111M00005542A:D09 MA242:D05 3239 3132 M00007031D:E02 MA240:F11 3240 3134M00007032A:D04 MA240:G11 3241 3135 M00005813C:F12 MA242:H11 3242 3171SL163 MA248:B05 3243 3173 SL164 MA248:C05 3244 3179 SL167 MA248:F05 32453181 SL168 MA248:G05 3246 3183 SL169 MA248:H05 3247 3231 M00023320B:A03MA36:H11 3248 3238 M00005350B:F10 MA246:C05 3249 3267 M00008069D:F01MA30:B05 3250 3268 M00022165B:C08 MA35:B05 3251 3272 M00022165C:E12MA35:D05 3252 3274 M00022166C:E07 MA35:E05 3253 3275 M00008072D:E12MA30:F05 3254 3282 M00022211B:D05 MA35:A11 3255 3293 M00008089A:E09MA30:G11 3256 3317 M00003974D:E04 MA24:C11 3257 3323 M00003980D:F10MA24:F11 3258 3327 M00003984D:C08 MA24:H11 3259 3370 M00023373D:A01MA22:E05 3260 3376 M00023396D:D01 MA22:H05 3261 3394 M00001437D:E12MA16:A05 3262 3396 M00001438A:B09 MA16:B05 3263 3401 M00001369A:C07MA14:E05 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M00042731A:G04 MA167:F093968 22718 M00042806C:E09 MA171:G09 3969 22720 M00042806D:F08 MA171:H093970 22725 M00056537A:F05 MA174:C03 3971 22727 M00056537D:A07 MA174:D033972 22734 RG:1862584:20001:G03 MA139:G03 3973 22737 M00056585D:D05MA174:A09 3974 22739 M00056586C:B08 MA174:B09 3975 22745 M00056592A:B08MA174:E09 3976 22757 RG:378550:10009:C03 MA158:C03 3977 22780RG:789040:10011:F09 MA160:F09 3978 22787 M00057283A:D01 MA182:B03 397922792 M00043505A:E07 MA184:D03 3980 22798 M00043506B:G10 MA184:G03 398122800 M00043507A:B02 MA184:H03 3982 22801 M00042353C:F02 MA182:A09 398322812 M00054516B:A08 MA184:F09 3984 22834 M00054986D:B04 MA198:A09 398522836 M00054987C:B10 MA198:B09 3986 22838 M00054988D:B11 MA198:C09 398722857 M00055743C:G08 MA170:E03 3988 22887 M00055196B:C09 MA196:D03 398922899 M00055238B:G05 MA196:B09 3990 22910 M00056207B:H06 MA180:G09 399122945 M00055966C:G04 MA179:A03 3992 22946 M00056920D:C08 MA177:A03 399322949 M00055969D:D01 MA179:C03 3994 22969 M00056055D:F06 MA179:E09 399522970 M00056956B:G12 MA177:E09 3996 22971 M00056060D:C04 MA179:F09 399722973 M00056061C:H04 MA179:G09 3998 22977 M00054743C:E05 MA188:A03 399922979 M00054744C:B02 MA188:B03 4000 22997 M00054808A:E02 MA188:C09 400123005 M00054811A:G01 MA188:G09 4002 23041 M00054797C:G10 MA168:A03 400323042 M00042843B:H01 MA172:A03 4004 23048 M00042844D:D10 MA172:D03 400523050 M00042845D:A12 MA172:E03 4006 23053 M00054800C:H10 MA168:G03 400723055 M00054911D:E09 MA168:H03 4008 23057 M00055450A:G03 MA168:A09 400923063 M00055456B:H05 MA168:D09 4010 23079 M00056733C:D03 MA175:D03 401123087 M00056737D:E08 MA175:H03 4012 23097 M00056809B:A12 MA175:E09 401323101 M00056809D:C07 MA175:G09 4014 23131 RG:1664308:10014:F09 MA163:F094015 23139 M00043321A:G07 MA183:B03 4016 23142 M00054549A:F03 MA185:C034017 23159 M00043381A:C08 MA183:D09 4018 23169 M00056642B:G03 MA186:A034019 23199 M00056688C:A07 MA186:H09 4020 23202 M00056257C:G03 MA181:A044021 23213 M00055545C:F11 MA169:G04 4022 23221 M00055653C:F04 MA169:C104023 23223 M00055653D:F01 MA169:D10 4024 23252 M00055385A:C11 MA197:B104025 23304 M00056157A:F11 MA180:D04 4026 23306 M00056160A:F03 MA180:E044027 23307 M00056426A:H07 MA173:F04 4028 23318 M00056214C:B04 MA180:C104029 23320 M00056216A:F10 MA180:D10 4030 23325 M00056507A:G11 MA173:G104031 23329 M00054648C:C10 MA187:A04 4032 23330 M00054862A:H11 MA189:A044033 23331 M00054648D:F12 MA187:B04 4034 23335 M00054650C:H08 MA187:D044035 23344 M00054868C:C11 MA189:H04 4036 23351 M00054700C:E02 MA187:D104037 23356 M00054902D:G11 MA189:F10 4038 23358 M00054903B:G06 MA189:G104039 23359 M00054706A:D05 MA187:H10 4040 23366 M00057207A:D05 MA193:C044041 23368 M00057207C:F06 MA193:D04 4042 23372 M00057208B:F11 MA193:F044043 23382 M00057242B:B10 MA193:C10 4044 23397 M00042555A:E06 MA167:C044045 23399 M00042561A:H03 MA167:D04 4046 23402 M00042756C:E10 MA171:E044047 23404 M00042758D:F01 MA171:F04 4048 23408 M00042759B:E02 MA171:H044049 23412 M00042808D:D03 MA171:B10 4050 23414 M00042808D:D10 MA171:C104051 23416 M00042811B:A05 MA171:D10 4052 23417 M00042746B:F05 MA167:E104053 23421 M00042746C:D01 MA167:G10 4054 23422 M00042812D:B04 MA171:G104055 23425 M00056546B:F12 MA174:A04 4056 23439 M00056550A:G09 MA174:H044057 23453 M00056610C:B08 MA174:G10 4058 23460 RG:745556:10011:B04MA160:B04 4059 23469 RG:446537:10009:G04 MA158:G04 4060 23475RG:375937:10009:B10 MA158:B10 4061 23476 RG:755120:10011:B10 MA160:B104062 23480 RG:781108:10011:D10 MA160:D10 4063 23505 M00042450C:H10MA182:A10 4064 23507 M00042451B:B05 MA182:B10 4065 23508 M00054517D:D12MA184:B10 4066 23544 M00055002B:G06 MA198:D10 4067 23555 M00055749A:C09MA170:B04 4068 23559 M00055750A:F10 MA170:D04 4069 23565 M00055757A:H06MA170:G04 4070 23591 M00055200B:F03 MA196:D04 4071 23595 M00055203B:F05MA196:F04 4072 23657 M00055980B:F12 MA179:E04 4073 23667 M00056066C:H10MA179:B10 4074 23669 M00056067B:F12 MA179:C10 4075 23671 M00056075D:H10MA179:D10 4076 23672 M00056962D:A05 MA177:D10 4077 23673 M00056081D:B09MA179:E10 4078 23674 M00056963A:E01 MA177:E10 4079 23675 M00056081D:C02MA179:F10 4080 23678 M00056964D:C08 MA177:G10 4081 23679 M00056084A:B08MA179:H10 4082 23683 M00054750C:G08 MA188:B04 4083 23685 M00054750D:F04MA188:C04 4084 23693 M00054757A:F05 MA188:G04 4085 23695 M00054760D:B10MA188:H04 4086 23746 M00042847A:A04 MA172:A04 4087 23748 M00042847A:D10MA172:B04 4088 23755 M00054917B:G02 MA168:F04 4089 23765 M00055468D:D05MA168:C10 4090 23767 M00055469B:E11 MA168:D10 4091 23773 M00055492C:C01MA168:G10 4092 23775 M00055496A:E06 MA168:H10 4093 23787 M00056742D:D01MA175:F04 4094 23805 M00056814D:C08 MA175:G10 4095 23827RG:1636303:10014:B10 MA163:B10 4096 23829 RG:1643142:10014:C10 MA163:C104097 23831 RG:1650444:10014:D10 MA163:D10 4098 23840RG:1418984:10003:H10 MA152:H10 4099 23841 M00043339C:C12 MA183:A04 410023843 M00043342C:H03 MA183:B04 4101 23847 M00043350A:C04 MA183:D04 410223875 M00056646D:G05 MA186:B04 4103 23880 M00055406C:H08 MA199:D04 410423887 M00056653C:F06 MA186:H04 4105 23888 M00055408A:H06 MA199:H04 410623905 M00055545D:E02 MA169:A05 4107 23909 M00055548B:H07 MA169:C05 410823912 M00056271C:F02 MA181:D05 4109 23915 M00055550D:A05 MA169:F05 411023929 M00055661A:F09 MA169:E11 4111 24003 M00056427D:A09 MA173:B05 411224004 M00056163C:H09 MA180:B05 4113 24005 M00056428B:F07 MA173:C05 411424006 M00056163D:E01 MA180:C05 4115 24009 M00056428C:A12 MA173:E05 411624011 M00056429D:D07 MA173:F05 4117 24014 M00056175D:B05 MA180:G05 411824017 M00056507D:D04 MA173:A11 4119 24027 M00056511D:H07 MA173:F11 412024033 M00054654A:F12 MA187:A05 4121 24034 M00054868D:F12 MA189:A05 412224039 M00054661B:H10 MA187:D05 4123 24043 M00054666B:C07 MA187:F05 412424044 M00054870B:H05 MA189:F05 4125 24045 M00054669B:B03 MA187:G05 412624049 M00054706B:G04 MA187:A11 4127 24055 M00054720C:F01 MA187:D11 412824057 M00054722B:E08 MA187:E11 4129 24058 M00054908A:H08 MA189:E11 413024061 M00054723B:H12 MA187:G11 4131 24070 M00057210B:G10 MA193:C05 413224084 M00057248D:B05 MA193:B11 4133 24092 M00057252A:F06 MA193:F11 413424099 M00042573B:A02 MA167:B05 4135 24108 M00042766A:E10 MA171:F05 413624113 M00042882D:G08 MA167:A11 4137 24115 M00042885C:A12 MA167:B11 413824116 M00042815A:E07 MA171:B11 4139 24118 M00042817B:E11 MA171:C11 414024121 M00042887C:A07 MA167:E11 4141 24126 M00042818D:A08 MA171:G11 414224133 M00056552A:G08 MA174:C05 4143 24135 M00056552C:D08 MA174:D05 414424137 M00056553C:E10 MA174:E05 4145 24143 M00056555B:C11 MA174:H05 414624151 M00056611C:D03 MA174:D11 4147 24155 M00056611D:B03 MA174:F11 414824157 M00056611D:F08 MA174:G11 4149 24159 M00056614C:F06 MA174:H11 415024161 RG:358387:10009:A05 MA158:A05 4151 24193 M00057302A:F08 MA182:A054152 24197 M00057302C:H09 MA182:C05 4153 24204 M00054496A:B09 MA184:F054154 24208 M00054496A:H05 MA184:H05 4155 24209 M00042460B:A08 MA182:A114156 24210 M00054524B:B09 MA184:A11 4157 24212 M00054526C:E05 MA184:B114158 24213 M00042516B:A08 MA182:C11 4159 24215 M00042517D:H10 MA182:D114160 24216 M00054527B:H11 MA184:D11 4161 24217 M00042517D:H11 MA182:E114162 24222 M00054529C:G04 MA184:G11 4163 24223 M00043300D:A06 MA182:H114164 24230 M00054958A:G10 MA198:C05 4165 24232 M00054958B:B07 MA198:D054166 24240 M00054961D:E08 MA198:H05 4167 24246 M00055015C:H02 MA198:C114168 24250 M00055016B:D03 MA198:E11 4169 24265 M00055764D:D05 MA170:E054170 24275 M00055815C:E08 MA170:B11 4171 24283 M00055819B:B12 MA170:F114172 24287 M00055820C:H11 MA170:H11 4173 24289 M00055204B:C04 MA196:A054174 24295 M00055209A:C09 MA196:D05 4175 24311 M00055252C:G12 MA196:D114176 24354 M00056934C:D08 MA177:A05 4177 24355 M00055989C:D03 MA179:B054178 24360 M00056937C:G12 MA177:D05 4179 24367 M00055997B:A02 MA179:H054180 24373 M00056087A:G01 MA179:C11 4181 24375 M00056091A:H05 MA179:D114182 24378 M00056966B:A05 MA177:E11 4183 24379 M00056093A:F08 MA179:F114184 24383 M00056096C:H10 MA179:H11 4185 24399 M00054766B:E10 MA188:H054186 24403 M00054817B:H09 MA188:B11 4187 24407 M00054818D:G04 MA188:D114188 24450 M00042851D:H04 MA172:A05 4189 24452 M00042853A:F01 MA172:B054190 24457 M00055426A:G06 MA168:E05 4191 24467 M00055496A:G12 MA168:B114192 24475 M00055509C:C02 MA168:F11 4193 24477 M00055510B:F08 MA168:G114194 24479 M00055510D:A08 MA168:H11 4195 24483 M00056748C:B08 MA175:B054196 24485 M00056749A:F01 MA175:C05 4197 24493 M00056754B:A10 MA175:G054198 24495 M00056754B:H06 MA175:H05 4199 24521 RG:1653390:10014:E05MA163:E05 4200 24525 RG:1669553:10014:G05 MA163:G05 4201 24547M00043355A:H12 MA183:B05 4202 24549 M00043355B:F10 MA183:C05 4203 24557M00043357B:B10 MA183:G05 4204 24558 M00054557C:D09 MA185:G05 4205 24559M00043358B:G11 MA183:H05 4206 24561 M00043396D:B04 MA183:A11 4207 24576M00054612D:D11 MA185:H11 4208 24578 M00055409B:D08 MA199:A05 4209 24580M00055409D:F06 MA199:B05 4210 24582 M00055410A:A06 MA199:C05 4211 24587M00056659A:D08 MA186:F05 4212 24599 M00056704C:H08 MA186:D11 4213 24609M00055553C:B06 MA169:A06 4214 24610 M00056280B:D10 MA181:A06 4215 24614M00056282D:G10 MA181:C06 4216 24622 M00056288B:A12 MA181:G06 4217 24627M00055686D:E11 MA169:B12 4218 24630 M00042346B:F09 MA181:C12 4219 24633M00055698C:E05 MA169:E12 4220 24634 M00042347C:D07 MA181:E12 4221 24635M00055702C:C04 MA169:F12 4222 24638 M00042348C:F03 MA181:G12 4223 24648M00055335D:E01 MA197:D06 4224 24708 M00056180C:E06 MA180:B06 4225 24712M00056184B:G11 MA180:D06 4226 24721 M00056514A:F06 MA173:A12 4227 24727M00056514C:H11 MA173:D12 4228 24741 M00054674D:C05 MA187:C06 4229 24743M00054675A:H07 MA187:D06 4230 24744 M00054878A:G12 MA189:D06 4231 24751M00054676B:D07 MA187:H06 4232 24755 M00054725A:E09 MA187:B12 4233 24758M00054924C:B09 MA189:C12 4234 24759 M00054726D:B04 MA187:D12 4235 24762M00054927A:H09 MA189:E12 4236 24763 M00054727C:F11 MA187:F12 4237 24767M00054728A:H05 MA187:H12 4238 24768 M00054930B:G05 MA189:H12 4239 24772M00057214C:G11 MA193:B06 4240 24776 M00057216C:G01 MA193:D06 4241 24780M00057217C:B07 MA193:F06 4242 24803 M00042695A:H04 MA167:B06 4243 24805M00042695D:D09 MA167:C06 4244 24808 M00042771A:D01 MA171:D06 4245 24810M00042772D:F02 MA171:E06 4246 24812 M00042773A:A12 MA171:F06 4247 24813M00042699B:B10 MA167:G06 4248 24817 M00042889A:H07 MA167:A12 4249 24818M00042819A:C09 MA171:A12 4250 24820 M00042819C:B03 MA171:B12 4251 24821M00042895B:C02 MA167:C12 4252 24822 M00042823B:A02 MA171:C12 4253 24825M00042895D:B04 MA167:E12 4254 24843 M00056564B:F11 MA174:F06 4255 24845M00056564C:E08 MA174:G06 4256 24849 M00056615D:A01 MA174:A12 4257 24861M00056620D:F02 MA174:G12 4258 24865 RG:359184:10009:A06 MA158:A06 425924887 RG:428530:10009:D12 MA158:D12 4260 24897 M00057310A:A07 MA182:A064261 24908 M00054503C:H10 MA184:F06 4262 24917 M00043302C:D03 MA182:C124263 24924 M00054535B:F10 MA184:F12 4264 24926 M00054535C:D10 MA184:G124265 24928 M00054535C:H09 MA184:H12 4266 24934 M00054964B:A08 MA198:C064267 24936 M00054966C:H01 MA198:D06 4268 24952 M00055022D:F01 MA198:D124269 24958 M00055026C:C12 MA198:G12 4270 24960 M00055027B:C11 MA198:H124271 24985 M00055826D:C11 MA170:E12 4272 24989 M00055828C:D10 MA170:G124273 24991 M00055828D:F12 MA170:H12 4274 24995 M00055215C:E11 MA196:B064275 24999 M00055217C:E09 MA196:D06 4276 25001 M00055221B:C01 MA196:E064277 25005 M00055222A:E02 MA196:G06 4278 25012 M00056226D:F03 MA180:B124279 25019 M00055258A:G02 MA196:F12 4280 25057 M00055998A:A02 MA179:A064281 25058 M00056945A:B11 MA177:A06 4282 25062 M00056945D:H03 MA177:C064283 25063 M00056001A:F11 MA179:D06 4284 25068 M00056946D:B04 MA177:F064285 25073 M00056101B:B02 MA179:A12 4286 25081 M00056110C:D09 MA179:E124287 25083 M00056111B:H03 MA179:F12 4288 25101 M00054772B:H06 MA188:G064289 25109 M00054825B:B05 MA188:C12 4290 25111 M00054831A:G04 MA188:D124291 25115 M00054831D:B07 MA188:F12 4292 25156 M00042862D:A12 MA172:B064293 25162 M00042864A:E05 MA172:E06 4294 25164 M00042864D:E06 MA172:F064295 25177 M00055514B:A05 MA168:E12 4296 25191 M00056763B:A12 MA175:D064297 25195 M00056767D:F06 MA175:F06 4298 25201 M00056821A:D08 MA175:A124299 25205 M00056822C:G03 MA175:C12 4300 25209 M00056823D:H02 MA175:E124301 25217 RG:1609994:10014:A06 MA163:A06 4302 25243RG:1667183:10014:F12 MA163:F12 4303 25249 M00043358D:C06 MA183:A06 430425250 M00054558B:E05 MA185:A06 4305 25257 M00043361B:G03 MA183:E06 430625277 M00043408C:D11 MA183:G12 4307 25280 M00054632A:E11 MA185:H12 430825281 M00056661A:G05 MA186:A06 4309 25283 M00056661C:C11 MA186:B06 431025284 M00055412D:E05 MA199:B06 4311 25286 M00055413A:G12 MA199:C06 431225288 M00055414D:A09 MA199:D06 4313 25301 M00056707B:C01 MA186:C12 431425317 M00056237D:C10 MA181:D01 4315 25319 M00056238B:D03 MA181:E01 431625323 M00056239B:D05 MA181:G01 4317 25325 M00056241B:H07 MA181:H01 431825380 I:2921194:04B02:C06 MA118:C06 4319 25388 I:1624865:04B02:G06MA118:G06 4320 25389 I:1728607:04A02:H06 MA116:H06 4321 25390I:2827453:04B02:H06 MA118:H06 4322 25398 I:2070593:04B02:D12 MA118:D124323 25405 I:2683114:04A02:H12 MA116:H12 4324 25419 I:1809336:02A02:G06MA108:G06

Characterization of Sequences

The sequences of the isolated polynucleotides were first masked toeliminate low complexity sequences using the RepeatMasker maskingprogram, publicly available through a web site supported by theUniversity of Washington (See also Smit, A. F. A. and Green, P.,unpublished results). Generally, masking does not influence the finalsearch results, except to eliminate sequences of relatively littleinterest due to their low complexity, and to eliminate multiple “hits”based on similarity to repetitive regions common to multiple sequences,e.g., Alu repeats. Masking resulted in the elimination of severalsequences.

The remaining sequences of the isolated polynucleotides were used in ahomology search of the GenBank database using the TeraBLAST program(TimeLogic, Crystal Bay, Nev.), a DNA and protein sequence homologysearching algorithm. TeraBLAST is a version of the publicly availableBLAST search algorithm developed by the National Center forBiotechnology, modified to operate at an accelerated speed withincreased sensitivity on a specialized computer hardware platform. Theprogram was run with the default parameters recommended by TimeLogic toprovide the best sensitivity and speed for searching DNA and proteinsequences. Gene assignment for the query sequences was determined basedon best hit form the GenBank database; expectancy values are providedwith the hit.

Summary of TeraBLAST Search Results

Table 32 provides information about the gene corresponding to eachpolynucleotide. Table 32 includes: (1) the “SEQ ID NO” of the sequence;(2) the “Clone ID” assigned to the clone from which the sequence wasisolated; (3) the “MAClone ID” assigned to the clone from which thesequence was isolated; (4) the percentage of masking of the sequence(“Mask Prcnt”) (5) the GenBank Accession Number of the publiclyavailable sequence corresponding to the polynucleotide (“GBHit”); (6) adescription of the GenBank sequence (“GBDescription”); and (7) the scoreof the similarity of the polynucleotide sequence and the GenBanksequence (“GBScore”). The published information for each GenBank and ESTdescription, as well as the corresponding sequence identified by theprovided accession number, are incorporated herein by reference.

TABLE 32 SEQ ID MAClone Mask NO Clone ID ID Prcnt GBHit GBDescriptionGBScore 3022 M00026919B:A10 MA40:F01 Z69708gi|1204106|emb|Z69708.1HSL241B9C 2.2E−208 Human DNA sequence from cosmidL241B9, Huntington's Disease Region, chromosome 4p16.3 contains pol 3023M00026919B:E07 MA40:G01 Y16675 gi|3378616|emb|Y16675.1HSCPRM1 0 Homosapiens mRNA for aflatoxin B1- aldehyde reductase 3024 M00026919D:F04MA40:H01 M62810 gi|188563|gb|M62810.1HUMMITF1   1E−300 Humanmitochondrial transcription factor 1 mRNA, complete cds 3025M00026914D:G06 MA40:A01 NM_020990 gi|11641403|ref|NM_020990.2 Homo2.3E−288 sapiens creatine kinase, mitochondrial 1 (ubiquitous) (CKMT1),nuclear gene encoding mitochondrial 3026 M00026950A:A09 MA40:D07BC010020 gi|14603100|gb|BC010020.1BC010020 9.3E−207 Homo sapiens,adaptor-related protein complex 3, sigma 2 subunit, clone MGC: 19643IMAGE: 2959670, 3027 M00003820C:A09 MA244:B01 0.83544 AK026527gi|10439404|dbj|AK026527.1AK026527 6.6E−24 Homo sapiens cDNA: FLJ22874fis, clone KAT02871 3028 M00001673A:G03 MA244:E01 BC018192gi|17390428|gb|BC018192.1BC018192 4.6E−274 Homo sapiens, inositol1,3,4-triphosphate 5/6 kinase, clone MGC: 21491 IMAGE: 3867269, mRNA,comple 3029 M00007939A:A12 MA27:B07 3030 M00007939A:B11 MA27:D07AK055664 gi|16550447|dbj|AK055664.1AK055664 6.7E−186 Homo sapiens cDNAFLJ31102 fis, clone IMR322000010 3031 M00007939B:G03 MA27:H07 BC006230gi|13623260|gb|BC006230.1BC006230 2.3E−151 Homo sapiens,lysophospholipase-like, clone MGC: 10338 IMAGE: 3945191, mRNA, completecds 3032 M00007997D:G08 MA29:C01 BC012323gi|15147375|gb|BC012323.1BC012323 2.1E−198 Homo sapiens, Similar to cut(Drosophila)- like 1 (CCAAT displacement protein), clone IMAGE: 4550603033 M00026894C:E11 MA39:F07 AF052955 gi|8117711|gb|AF052955.1AF052955  9E−204 Homo sapiens F1-ATPase epsilon-subunit (ATP5E) mRNA, completecds; nuclear gene for mitochondrial 3034 M00001391A:C05 MA15:G01AK000140 gi|7020034|dbj|AK000140.1AK000140 2.2E−107 Homo sapiens cDNAFLJ20133 fis, clone COL06539 3035 M00006818A:A06 MA240:C01 0.06554AL136706 gi|12052931|emb|AL136706.1HSM801674 9.2E−248 Homo sapiens mRNA;cDNA DKFZp566B2024 (from clone DKFZp566B2024); complete cds 3036M00023278A:F09 MA36:E01 3037 M00023299A:G01 MA36:C07 3038 M00023301A:A11MA36:F07 BC007270 gi|13938284|gb|BC007270.1BC007270   1E−300 Homosapiens, clone MGC: 15585 IMAGE: 3160319, mRNA, complete cds 3039M00008050A:D12 MA30:C01 BC015839 gi|16198382|gb|BC015839.1BC0158391.6E−267 Homo sapiens, clone IMAGE: 4296901, mRNA 3040 M00022135A:C04MA35:F01 BC007925 gi|14043985|gb|BC007925.1BC007925 1.3E−124 Homosapiens, retinoid X receptor, alpha, clone MGC: 14451 IMAGE: 4304205,mRNA, complete cds 3041 M00022137A:A05 MA35:G01 AK025549gi|10438098|dbj|AK025549.1AK025549 1.6E−267 Homo sapiens cDNA: FLJ21896fis, clone HEP03441 3042 M00022176C:A07 MA35:A07 BC000393gi|12653248|gb|BC000393.1BC000393 2.4E−183 Homo sapiens, Similar to CAAXbox 1, clone MGC: 8471 IMAGE: 2821721, mRNA, complete cds 3043M00008077B:A08 MA30:D07 U09564 gi|507212|gb|U09564.1HSU09564 Human6.3E−211 serine kinase mRNA, complete cds 3044 M00008077C:D09 MA30:G07U50939 gi|1314559|gb|U50939.1HSU50939 1.4E−258 Human amyloid precursorprotein-binding protein 1 mRNA, complete cds 3045 M00022081C:E09MA34:F01 AJ271408 gi|6729589|emb|AJ271408.1HSA271408   1E−237 Homosapiens mRNA for Fas-associated factor, FAF1 (Faf1 gene) 3046M00001662A:G06 MA24:H01 BC006229 gi|13623258|gb|BC006229.1BC0062291.6E−264 Homo sapiens, cytochrome c oxidase subunit Vb, clone MGC: 10622IMAGE: 3952882, mRNA, complete cds 3047 M00022102B:B11 MA34:D07 AJ250229gi|8926686|emb|AJ250229.1HSA250229 0 Homo sapiens mRNA for chromosome 11hypothetical protein (ORF1) 3048 M00022102B:E08 MA34:E07 3049M00022569D:G06 MA22:F01 0.0572 U08839 gi|517197|gb|U08839.1HSU08839Human 6.7E−233 urokinase-type plasminogen activator receptor mRNA,complete cds 3050 M00001358B:B11 MA14:A01 AB047848gi|11094286|dbj|AB047848.1AB047848 4.3E−299 Homo sapiens mRNA forzetal-COP, complete cds 3051 M00001429A:G04 MA16:A01 BC000491gi|12653440|gb|BC000491.1BC000491 0 Homo sapiens, proliferating cellnuclear antigen, clone MGC: 8367 IMAGE: 2820036, mRNA, complete cd 3052M00001358B:F05 MA14:B01 BC000706 gi|12653834|gb|BC000706.1BC0007061.1E−299 Homo sapiens, Similar to G8 protein, clone MGC: 1225 IMAGE:3349773, mRNA, complete cds 3053 M00001429C:C03 MA16:C01 X16064gi|37495|emb|X16064.1HSTUMP Human 0 mRNA for translationally controlledtumor protein 3054 M00001359D:B04 MA14:E01 AK000481gi|7020597|dbj|AK000481.1AK000481   1E−300 Homo sapiens cDNA FLJ20474fis, clone KAT07183 3055 M00001360A:E10 MA14:F01 BC002899gi|12804092|gb|BC002899.1BC002899 6.4E−267 Homo sapiens, protein(peptidyl-prolyl cis/trans isomerase) NIMA-interacting 1, clone MGC:10717 I 3056 M00001360C:B05 MA14:G01 NM_001014gi|13904867|ref|NM_001014.2 Homo 2.1E−282 sapiens ribosomal protein S10(RPS 10), mRNA 3057 M00001430B:F01 MA16:G01 AL050096gi|4884121|emb|AL050096.1HSM800178 6.9E−47 Homo sapiens mRNA; cDNADKFZp586A0419 (from clone DKFZp586A0419); partial cds 3058M00001430C:A02 MA16:H01 AF083248 gi|5106790|gb|AF083248.1AF083248 0 Homosapiens ribosomal protein L26 homolog mRNA, complete cds 3059M00001445C:H05 MA16:A07 X02152 gi|34312|emb|X02152.1HSLDHAR 0 Human mRNAfor lactate dehydrogenase- A (LDH-A, EC 1.1.1.27) 3060 M00001445D:D07MA16:B07 X73458 gi|312997|emb|X73458.1HSPLK1 2.7E−266 H. sapiens plk-1mRNA 3061 M00001374D:D10 MA14:G07 BC018620gi|17391359|gb|BC018620.1BC018620 8.3E−254 Homo sapiens, Similar to ADP-ribosyltransferase (NAD+; poly (ADP- ribose) polymerase), clone IMAGE3062 M00001375A:A08 MA14:H07 AF231705 gi|8745393|gb|AF231705.1AF2317054.1E−137 Homo sapiens Alu co-repressor 1 (ACR1) mRNA, complete cds 3063M00006600A:E07 MA241:B01 AK001635 gi|7023008|dbj|AK001635.1AK0016353.2E−281 Homo sapiens cDNA FLJ10773 fis, clone NT2RP4000246, moderatelysimilar to NPC DERIVED PROLINE RIC 3064 M00006690A:F06 MA241:C07 0.281523065 M00023325D:A08 MA37:B02 BC001901 gi|12804898|gb|BC001901.1BC0019012.7E−294 Homo sapiens, BCL2-antagonist of cell death, clone MGC: 2100IMAGE: 3537914, mRNA, complete cds 3066 M00026921D:F12 MA40:C02 AK054686gi|16549280|dbj|AK054686.1AK054686 0 Homo sapiens cDNA FLJ30124 fis,clone BRACE1000093, highly similar to TNF RECEPTOR ASSOCIATED FA 3067M00023325D:F06 MA37:D02 0.15781 BC017660gi|17389200|gb|BC017660.1BC017660 1.2E−188 Homo sapiens, clone MGC:14608 IMAGE: 4049404, mRNA, complete cds 3068 M00026924A:E09 MA40:G02AL359938 gi|8977893|emb|AL359938.1HSM802719 0 Homo sapiens mRNA; cDNADKFZp547H236 (from clone DKFZp547H236) 3069 M00007940C:A04 MA27:D08AF381986 gi|17985445|gb|AF381986.1AF381986 1.6E−264 Homo sapienshaplotype X mitochondrion, complete genome 3070 M00007941C:H03 MA27:F08U97519 gi|2213812|gb|U97519.1HSU97519 Homo 4.5E−271 sapienspodocalyxin-like protein mRNA, complete cds 3071 M00021638B:F03 MA31:F08NM_004417 gi|7108342|ref|NM_004417.2 Homo 3.2E−250 sapiens dualspecificity phosphatase 1 (DUSP1), mRNA 3072 M00007941D:C04 MA27:H08AL110202 gi|5817121|emb|AL110202.1HSM800854 2.5E−263 Homo sapiens mRNA;cDNA DKFZp586I2022 (from clone DKFZp586I2022) 3073 M00004054D:D020.19296 3074 M00001507A:A10 MA23:E08 AF220656gi|7107358|gb|AF220656.1AF220656 1.4E−255 Homo sapiensapoptosis-associated nuclear protein PHLDA1 (PHLDA1) mRNA, partial cds3075 M00004198D:A01 AY007138 gi|9956042|gb|AY007138.1 Homo sapiens 0clone CDABP0061 mRNA sequence 3076 M00001528C:B08 MA23:G08 AF106066gi|5353548|gb|AF106066.1AF106066 4.1E−28 Homo sapiens RAD17 pseudogene,complete sequence 3077 M00008002C:A05 MA29:B03 AB023173gi|4589555|dbj|AB023173.1AB023173 1.6E−292 Homo sapiens mRNA forKIAA0956 protein, partial cds 3078 M00008006C:H05 MA29:H03 AF327923gi|13241760|gb|AF327923.1AF327923 8.2E−205 Homo sapiens transmembraneprotein induced by tumor necrosis factor alpha (TMPIT) mRNA, complete3079 M00026850C:A01 MA39:A02 AK055812 gi|16550635|dbj|AK055812.1AK0558128.5E−66 Homo sapiens cDNA FLJ31250 fis, clone KIDNE2005336, weaklysimilar to Homo sapiens antigen NY-CO 3080 M00026853D:C07 MA39:F020.27143 AF212248 gi|13182770|gb|AF212248.1AF212248 1.9E−153 Homo sapiensCDA09 mRNA, complete cds 3081 M00026896A:C09 MA39:D08 AK018953gi|12858931|dbj|AK018953.1AK018953 3.9E−139 Mus musculus adult maletestis cDNA, RIKEN full-length enriched library, clone: 1700111D04, full3082 M00001391B:D02 MA15:C02 D86956 gi|1503985|dbj|D86956.1D86956 Human4.7E−221 mRNA for KIAA0201 gene, complete cds 3083 M00001391B:H05MA15:E02 AL110153 gi|5817055|emb|AL110153.1HSM800798   1E−300 Homosapiens mRNA; cDNA DKFZp586E0524 (from clone DKFZp586E0524) 3084M00001391D:C07 MA15:F02 AL136593 gi|7018431|emb|AL136593.1HSM801567 0Homo sapiens mRNA; cDNA DKFZp761K102 (from clone DKFZp761K102); completecds 3085 M00001392B:B01 MA15:G02 M73791 gi|189265|gb|M73791.1HUMANOVGENE3.5E−94 Human novel gene mRNA, complete cds 3086 M00001407B:C03 MA15:E08BC005116 gi|13477284|gb|BC005116.1BC005116   1E−300 Homo sapiens,structure specific recognition protein 1, clone MGC: 1608 IMAGE:3536048, mRNA, compl 3087 M00005635B:E02 MA242:B08 0.86798 3088M00005636B:B06 MA242:E08 AK008041 gi|12841981|dbj|AK008041.1AK0080411.5E−24 Mus musculus adult male small intestine cDNA, RIKEN full-lengthenriched library, clone: 2010002G 3089 M00006971A:E06 MA240:E08NM_002403 gi|9665260|ref|NM_002403.2 Homo 4.7E−274 sapiensmicrofibrillar-associated protein 2 (MFAP2), transcript variant 2, mRNA3090 M00005636D:B08 MA242:F08 3091 M00023302C:A04 MA36:B08 AF202922gi|13540826|gb|AF202922.2AF202922 4.6E−231 Homo sapiens LRP16 (LRP16)mRNA, complete cds 3092 M00023305A:C02 MA36:G08 3093 M00022180A:E08MA35:B08 BC018918 gi|17511926|gb|BC018918.1BC018918 3.6E−203 Homosapiens, clone MGC: 12603 IMAGE: 4130906, mRNA, complete cds 3094M00022181C:H11 MA35:E08 AK001485 gi|7022770|dbj|AK001485.1AK0014851.6E−161 Homo sapiens cDNA FLJ10623 fis, clone NT2RP2005520, highlysimilar to Homo sapiens chromosome-ass 3095 M00001673A:C11 U15128gi|902744|gb|U15128.1HSU15128 Human 0beta-1,2-N-acetylglucosaminyltransferase II (MGAT2) gene, complete cds3096 M00003853B:C07 BC008378 gi|14249982|gb|BC008378.1BC008378 2.4E−207Homo sapiens, programmed cell death 2, clone MGC: 12347 IMAGE: 4102043,mRNA, complete cds 3097 M00022106B:D04 MA34:B08 AB055387gi|12862374|dbj|AB055387.1AB055387 1.4E−86 Homo sapiens mitochondrialDNA 3098 M00003858B:G01 MA24:E08 0.26044 3099 M00022109B:A11 MA34:G08AK023237 gi|10435081|dbj|AK023237.1AK023237 0 Homo sapiens cDNA FLJ13175fis, clone NT2RP3003842 3100 M00022921A:H05 MA22:F02 0.11424 BC002976gi|12804234|gb|BC002976.1BC002976 0 Homo sapiens, Similar to cytochromeb- 561, clone MGC: 2190 IMAGE: 3535771, mRNA, complete cds 3101M00001430D:H07 MA16:A02 X58965 gi|35069|emb|X58965.1HSNM23H2G 1.9E−276H. sapiens RNA for nm23-H2 gene 3102 M00001360D:H10 MA14:B02 NM_002415gi|4505184|ref|NM_002415.1 Homo 6.2E−158 sapiens macrophage migrationinhibitory factor (glycosylation-inhibiting factor) (MIF), mRNA 3103M00001431A:E01 MA16:B02 AK026534 gi|10439413|dbj|AK026534.1AK026534  1E−300 Homo sapiens cDNA: FLJ22881 fis, clone KAT03571, highly similarto HUMFERL Human ferritin L chai 3104 M00001361A:A02 MA14:C02 NM_004053gi|15208644|ref|NM_004053.2 Homo 6.7E−270 sapiens bystin-like (BYSL),mRNA 3105 M00001362A:B03 MA14:H02 L47277 gi|986911|gb|L47277.1HUMTOPATRA  1E−296 Homo sapiens (cell line HepG2, HeLa) alpha topoisomerasetruncated-form mRNA, 3′UTR 3106 M00001376C:C01 MA14:A08 S73591gi|688296|gb|S73591.1S73591 Homo 5.8E−233 sapiens brain-expressedHHCPA78 homolog VDUP1 (Gene) mRNA, complete cds 3107 M00001449A:D02MA16:B08 BC013954 gi|15530314|gb|BC013954.1BC013954 9.6E−291 Homosapiens, clone IMAGE: 3505920, mRNA 3108 M00001378B:A02 MA14:C08BC002343 gi|12803082|gb|BC002343.1BC002343 5.2E−124 Homo sapiens,Similar to nucleolin, clone MGC: 8580 IMAGE: 2960982, mRNA, complete cds3109 M00001450A:D12 MA16:C08 AF106622 gi|4378528|gb|AF106622.1AF106622  5E−280 Homo sapiens mitochondrial inner membrane preproteintranslocase Tim17a mRNA, nuclear gene encodin 3110 M00001378C:D08MA14:D08 0.06114 BC002569 gi|12803486|gb|BC002569.1BC002569   3E−235Homo sapiens, ribosomal protein S4, X- linked, clone MGC: 2328 IMAGE:3139352, mRNA, complete cds 3111 M00001451D:F01 MA16:G08 BC001432gi|12655154|gb|BC001432.1BC001432 0 Homo sapiens, heterogeneous nuclearribonucleoprotein F, clone MGC: 2197 IMAGE: 3138435, mRNA, comp 3112M00006628B:A02 MA241:C02 NM_005826 gi|14141188|ref|NM_005826.2 Homo4.9E−80 sapiens heterogeneous nuclear ribonucleoprotein R (HNRPR), mRNA3113 M00026926C:F03 MA40:B03 AK027855 gi|14042836|dbj|AK027855.1AK0278551.1E−215 Homo sapiens cDNA FLJ14949 fis, clone PLACE2000341, highlysimilar to Homo sapiens sodium-depend 3114 M00026963B:H03 MA40:A09BC014557 gi|17939595|gb|BC014557.1BC014557 2.6E−241 Homo sapiens, cloneIMAGE: 3837222, mRNA 3115 M00026964A:E10 MA40:D09 NM_013375gi|17572813|ref|NM_013375.2 Homo 1.5E−171 sapiens TATA-bindingprotein-binding protein (ABT1), mRNA 3116 M00026965C:A11 MA40:F090.07092 AK054883 gi|16549505|dbj|AK054883.1AK054883   1E−176 Homosapiens cDNA FLJ30321 fis, clone BRACE2006281 3117 M00001398A:D11MA244:C09 BC009503 gi|14550505|gb|BC009503.1BC009503   1E−300 Homosapiens, G1 to S phase transition 1, clone MGC: 1735 IMAGE: 2822947,mRNA, complete cds 3118 M00008095C:H08 MA31:D03 BC000820gi|12654032|gb|BC000820.1BC000820 5.3E−255 Homo sapiens, menage a trois1 (CAK assembly factor), clone MGC: 5154 IMAGE: 3453943, mRNA, complet3119 M00007942A:F12 MA27:B09 NM_001102 gi|12025669|ref|NM_001102.2 Homo2.3E−257 sapiens actinin, alpha 1 (ACTN1), mRNA 3120 M00004212B:B12MA25:A09 0.11538 D38112 gi|644480|dbj|D38112.1HUMMTA Homo 2.4E−48sapiens mitochondrial DNA, complete sequence 3121 M00008014C:E11MA29:D05 0.05435 AL080111 gi|5262538|emb|AL080111.1HSM800619 1.7E−292Homo sapiens mRNA; cDNA DKFZp586G2222 (from clone DKFZp586G2222) 3122M00008015A:B05 MA29:E05 M23161 gi|339899|gb|M23161.1HUMTRANSC 1.3E−157Human transposon-like element mRNA 3123 M00022049A:B08 MA33:A05 AK001731gi|7023175|dbj|AK001731.1AK001731 5.8E−286 Homo sapiens cDNA FLJ10869fis, clone NT2RP4001677 3124 M00026856B:F08 MA39:A03 AK023351gi|10435249|dbj|AK023351.1AK023351 1.7E−298 Homo sapiens cDNA FLJ13289fis, clone OVARC1001170 3125 M00026856C:H12 MA39:B03 0.55489 3126M00026900D:A03 MA39:F09 NM_000995 gi|16117786|ref|NM_000995.2 Homo3.5E−200 sapiens ribosomal protein L34 (RPL34), transcript variant 1,mRNA 3127 M00026900D:C12 MA39:G09 BC014377gi|15680094|gb|BC014377.1BC014377 1.2E−274 Homo sapiens, clone IMAGE:4041545, mRNA, partial cds 3128 M00026901D:A03 MA39:H09 AK057845gi|16553806|dbj|AK057845.1AK057845 3.6E−178 Homo sapiens cDNA FLJ25116fis, clone CBR05731, highly similar to EPHRIN-A1 PRECURSOR 3129M00001393A:G03 MA15:E03 NM_001015 gi|14277698|ref|NM_001015.2 Homo 0sapiens ribosomal protein S11 (RPS11), mRNA 3130 M00001409B:D03 MA15:D09AF104914 gi|4206125|gb|AF104914.1AF104914 0 Homo sapiens map 3p22; 9.65cR from CHLC.GATA87B02 repeat region, complete sequence 3131M00001409B:G01 MA15:E09 Z69043 gi|2398656|emb|Z69043.1HSTRAPRNA 3.1E−278H. sapiens mRNA translocon-associated protein delta subunit precursor3132 M00001410C:C09 MA15:F09 BC007261 gi|13938270|gb|BC007261.1BC0072615.3E−252 Homo sapiens, clone MGC: 15545 IMAGE: 3050745, mRNA, completecds 3133 M00001410D:A03 MA15:G09 X52003 gi|311379|emb|X52003.1HSPS2MKN3.9E−265 H. sapiens pS2 protein gene 3134 M00005504D:F06 MA242:A030.33179 AK026112 gi|10438858|dbj|AK026112.1AK026112   5E−144 Homosapiens cDNA: FLJ22459 fis, clone HRC10045 3135 M00005510D:H10 MA242:G033136 M00006990D:D06 MA240:G09 M79321 gi|187270|gb|M79321.1HUMLYNTK3.8E−290 Human Lyn B protein mRNA, complete cds 3137 SL146 MA248:A030.09302 AF415176 gi|16589066|gb|AF415176.1AF415176 7.8E−92 Homo sapiensCSGEF (SGEF) mRNA, complete cds, alternatively spliced 3138 SL153MA248:H03 3139 SL198 MA248:E09 0.45185 BC008180gi|14198240|gb|BC008180.1BC008180 8.2E−115 Homo sapiens, DKFZP586A0522protein, clone MGC: 5320 IMAGE: 2900478, mRNA, complete cds 3140 SL199MA248:F09 AF415176 gi|16589066|gb|AF415176.1AF415176 6.2E−92 Homosapiens CSGEF (SGEF) mRNA, complete cds, alternatively spliced 3141SL200 MA248:G09 BC005307 gi|13529043|gb|BC005307.1BC005307 3.1E−191 Homosapiens, kallikrein 3, (prostate specific antigen), clone MGC: 12378IMAGE: 3950475, mRNA, com 3142 M00023283D:C03 MA36:C03 AF070673gi|3978241|gb|AF070673.1AF070673 3.7E−181 Homo sapiens stannin mRNA,complete cds 3143 M00023283D:D03 MA36:D03 Z69881gi|1524091|emb|Z69881.1HSSERCA3M 1.1E−299 H. sapiens mRNA for adenosinetriphosphatase, calcium 3144 M00023284A:D09 MA36:E03 AK024338gi|10436699|dbj|AK024338.1AK024338   1E−300 Homo sapiens cDNA FLJ14276fis, clone PLACE1005128 3145 M00023285D:C05 MA36:H03 U34877gi|1143231|gb|U34877.1HSU34877 Homo 6.5E−295 sapiens biliverdin-IX alphareductase mRNA, complete cds 3146 M00023306C:H11 MA36:A09 BC003366gi|13097197|gb|BC003366.1BC003366 0 Homo sapiens, calcium-regulatedheat- stable protein (24 kD), clone MGC: 5235 IMAGE: 2900952, mRNA, c3147 M00023308D:B06 MA36:C09 M57730 gi|179320|gb|M57730.1HUMB61 Human2.1E−176 B61 mRNA, complete cds 3148 M00023309D:H04 MA36:E09 AL136720gi|12052958|emb|AL136720.1HSM801688 0 Homo sapiens mRNA; cDNADKFZp566J2046 (from clone DKFZp566J2046); complete cds 3149M00023310A:D07 MA36:F09 AL359587 gi|8655647|emb|AL359587.1HSM802689 0Homo sapiens mRNA; cDNA DKFZp762M115 (from clone DKFZp762M115) 3150M00008079C:H04 MA30:B09 AF201943 gi|9295189|gb|AF201943.1AF2019435.6E−258 Homo sapiens HAH-P (HAH-P) mRNA, complete cds 3151M00008080B:B10 MA30:F09 D50683 gi|1827474|dbj|D50683.1D50683 Homo1.3E−224 sapiens mRNA for TGF-betaIIR alpha, complete cds 3152M00022198D:C02 MA35:F09 BC001546 gi|16306729|gb|BC001546.1BC001546  1E−300 Homo sapiens, Similar to RIKEN cDNA 1110064N10 gene, clone MGC:4924 IMAGE: 3462041, mRNA, complete 3153 M00022198D:G03 MA35:G09 X54199gi|31641|emb|X54199.1HSGAGMR 1.1E−231 Human mRNA for GARS-AIRS-GART 3154M00003768B:B09 MA24:D03 M32308 gi|202453|gb|M32308.1MUSZFXAA 2.4E−103Mouse zinc finger protein (Zfx) mRNA, complete cds, clone pDP1115 3155M00022110C:A08 MA34:C09 AK026894 gi|10439861|dbj|AK026894.1AK0268949.2E−288 Homo sapiens cDNA: FLJ23241 fis, clone COL01375 3156M00003886C:H08 MA24:E09 0.36691 AK056001gi|16550873|dbj|AK056001.1AK056001 7.9E−146 Homo sapiens cDNA FLJ31439fis, clone NT2NE2000707 3157 M00023297B:A10 MA22:D03 M33376gi|187444|gb|M33376.1HUMMCDR2 0 Human pseudo-chlordecone reductase mRNA,complete cds 3158 M00023314C:G05 MA22:G03 D87071gi|1510142|dbj|D87071.1D87071 Human 1.7E−178 mRNA for KIAA0233 gene,complete cds 3159 M00001363B:C04 MA14:D03 AY007220gi|9945039|gb|AY007220.1 Homo sapiens 1.8E−120 S100-type calcium bindingprotein A14 mRNA, complete cds 3160 M00001434D:F08 MA16:D03 NM_000852gi|6552334|ref|NM_000852.2 Homo   1E−300 sapiens glutathioneS-transferase pi (GSTP1), mRNA 3161 M00001435B:A04 MA16:E03 X99920gi|1694827|emb|X99920.1HSS100A13 1.1E−265 H. sapiens mRNA for S100calcium- binding protein A13 3162 M00001435B:B09 MA16:F03 Y00433gi|31917|emb|Y00433.1HSGSHPX Human 8.4E−226 mRNA for glutathioneperoxidase (EC 1.11.1.9.) 3163 M00001435C:F08 MA16:H03 BC006498gi|13676331|gb|BC006498.1BC006498   1E−300 Homo sapiens, ribonucleotidereductase M1 polypeptide, clone MGC: 2326 IMAGE: 2989344, mRNA, comple3164 M00001381A:F03 MA14:A09 BC007590 gi|14043203|gb|BC007590.1BC0075904.8E−246 Homo sapiens, ribosomal protein, large, P1, clone MGC: 15616IMAGE: 3343021, mRNA, complete cds 3165 M00001453B:E11 MA16:B09 BC001182gi|12654686|gb|BC001182.1BC001182   1E−300 Homo sapiens, clone MGC: 2616IMAGE: 3357266, mRNA, complete cds 3166 M00001453C:D02 MA16:D09 BC007435gi|13938568|gb|BC007435.1BC007435   1E−300 Homo sapiens, RNA bindingmotif protein, X chromosome, clone MGC: 4146 IMAGE: 3010123, mRNA,comple 3167 M00007121D:A05 MA243:A03 BC012816gi|15215444|gb|BC012816.1BC012816   1E−300 Homo sapiens, TGFB-inducedfactor 2 (TALE family homeobox), clone MGC: 4139 IMAGE: 2964507, mRNA, c3168 M00007122C:F03 MA243:B03 BC001866 gi|12804840|gb|BC001866.1BC0018666.4E−227 Homo sapiens, replication factor C (activator 1) 5 (36.5 kD),clone MGC: 1155 IMAGE: 3544137, mRNA, 3169 M00006638A:G02 MA241:C03J05036 gi|181193|gb|J05036.1HUMCTSE Human 6.7E−153 cathepsin E mRNA,complete cds 3170 M00006639B:H09 MA241:F03 0.36075 BC014188gi|15559664|gb|BC014188.1BC014188 5.6E−135 Homo sapiens, Similar togolgi autoantigen, golgin subfamily a, 2, clone MGC: 20672 IMAGE:4644480, 3171 M00007127C:C11 MA243:H03 AB020718gi|4240310|dbj|AB020718.1AB020718 0 Homo sapiens mRNA for KIAA0911protein, complete cds 3172 M00006720D:C11 MA241:E09 AF242773gi|7638246|gb|AF242773.1AF242773 1.2E−218 Homo sapiens mesenchymal stemcell protein DSCD75 mRNA, complete cds 3173 M00006728C:E07 MA241:F09L05093 gi|401844|gb|L05093.1HUMRIBPROD 0 Homo sapiens ribosomal proteinL18a mRNA, complete cds 3174 M00026931D:E08 MA40:F04 AK056187gi|16551522|dbj|AK056187.1AK056187 2.9E−275 Homo sapiens cDNA FLJ31625fis, clone NT2RI2003304 3175 M00026932D:B08 MA40:G04 NM_022553gi|15022812|ref|NM_022553.2 Homo   1E−300 sapiens SAC2 (suppressor ofactin mutations 2, yeast, homolog)-like (SACM2L), mRNA 3176M00026969D:D02 MA40:D10 0.05447 AK027681gi|14042541|dbj|AK027681.1AK027681 6.5E−159 Homo sapiens cDNA FLJ14775fis, clone NT2RP4000185 3177 M00023393B:E02 MA37:E10 BC001449gi|12655184|gb|BC001449.1BC001449 9.4E−157 Homo sapiens, heterogeneousnuclear ribonucleoprotein R, clone MGC: 2039 IMAGE: 3139052, mRNA, comp3178 M00003782D:D06 MA244:E04 BC000705 gi|12653832|gb|BC000705.1BC0007051.6E−295 Homo sapiens, clone MGC: 861 IMAGE: 3349507, mRNA, complete cds3179 M00004105D:B04 MA244:G04 AK056461gi|16551872|dbj|AK056461.1AK056461   1E−300 Homo sapiens cDNA FLJ31899fis, clone NT2RP7004173 3180 M00001556D:B11 MA244:D10 0.46689 3181M00021664B:G03 MA31:E10 0.87158 3182 M00004078A:A07 0.47872 3183M00001561A:B03 MA23:D10 AF090935 gi|6690235|gb|AF090935.1AF0909353.4E−256 Homo sapiens clone HQ0569 3184 M00008023C:A06 MA29:F07 U79296gi|1710278|gb|U79296.1HSU79296 2.2E−257 Human dihydrolipoamide acetyltransferase mRNA, partial cds 3185 M00008024C:F02 MA29:G07 0.26504AF092737 gi|4741762|gb|AF092737.1AF092737 3.5E−170 Homo sapiensubiquitously expressed transcript (UXT) mRNA, complete cds 3186M00008024C:G06 MA29:H07 BC017335 gi|16878274|gb|BC017335.1BC017335  1E−300 Homo sapiens, clone MGC: 29782 IMAGE: 4642600, mRNA, completecds 3187 M00022057C:H10 MA33:B07 AK027629gi|14042438|dbj|AK027629.1AK027629 6.8E−79 Homo sapiens cDNA FLJ14723fis, clone NT2RP3001708, weakly similar to TWISTED GASTRULATION PROTE3188 M00022059B:B06 MA33:C07 BC005267 gi|14710008|gb|BC005267.1BC005267  1E−300 Homo sapiens, clone IMAGE: 3683864, mRNA 3189 M00026902B:F10MA39:B10 L15203 gi|402482|gb|L15203.1HUMP1BX Human 4.8E−249 secretoryprotein (P1.B) mRNA, complete cds 3190 M00001394D:B08 MA15:C04 U58773gi|6502504|gb|U58773.1HSU58773   1E−300 Human calcium binding proteinmRNA, complete cds 3191 M00001415A:G05 MA15:A10 BC006337gi|3623468|gb|BC006337.1BC006337 1.5E−205 Homo sapiens, clone MGC: 12798IMAGE: 4304127, mRNA, complete cds 3192 M00001416B:E03 MA15:B10 X57198gi|37071|emb|X57198.1HSTFIIS Human 0 TFIIS mRNA for transcriptionelongation factor 3193 M00001421B:B12 MA15:H10 AF083246gi|5106786|gb|AF083246.1HSPC028 0 Homo sapiens HSPC028 mRNA, completecds 3194 M00005528C:E02 MA242:G04 AK054675gi|16549267|dbj|AK054675.1AK054675 1.5E−286 Homo sapiens cDNA FLJ30113fis, clone BNGH42000474 3195 M00023312D:F10 MA36:A10 0.47266 3196M00022157A:C06 MA35:C04 0.05831 3197 M00022165A:A11 MA35:H04 AK000084gi|7019941|dbj|AK000084.1AK000084 0 Homo sapiens cDNA FLJ20077 fis,clone COL02904 3198 M00022206A:B10 MA35:D10 AL137546gi|6808228|emb|AL137546.1HSM802283   1E−293 Homo sapiens mRNA; cDNADKFZp434A1920 (from clone DKFZp434A1920); partial cds 3199M00003811B:F09 BC009470 gi|14495716|gb|BC009470.1BC009470 0 Homosapiens, protein kinase, interferon- inducible double stranded RNAdependent activator, clone 3200 M00003812D:A11 AK026526gi|10439403|dbj|AK026526.1AK026526 7.6E−137 Homo sapiens cDNA: FLJ22873fis, clone KAT02673, highly similar to HUML12A Human ribosomal prote3201 M00022088D:C10 MA34:G04 3202 M00003910B:C12 AF132945gi|4680660|gb|AF132945.1AF132945 0 Homo sapiens CGI-11 protein mRNA,complete cds 3203 M00001366A:F06 MA14:A04 U24704gi|2078477|gb|U24704.1HSU24704 0 Human antisecretory factor-1 mRNA,complete cds 3204 M00001435C:F12 MA16:B04 BC003576gi|13097755|gb|BC003576.1BC003576   1E−300 Homo sapiens, actinin, alpha1, clone MGC: 2358 IMAGE: 3547017, mRNA, complete cds 3205M00001436B:E11 MA16:C04 BC003573 gi|13097746|gb|BC003573.1BC003573 0Homo sapiens, farnesyl-diphosphate farnesyltransferase 1, clone MGC:2200 IMAGE: 3538137, mRNA, com 3206 M00001366B:E01 MA14:D04 AK000609gi|7020817|dbj|AK000609.1AK000609   1E−300 Homo sapiens cDNA FLJ20602fis, clone KAT07189 3207 M00001436C:C03 MA16:D04 Z37986gi|780262|emb|Z37986.1HSPHBIPRM   1E−300 H. sapiens mRNA forphenylalkylamine binding protein 3208 M00001437A:B01 MA16:F04 NM_000994gi|15812220|ref|NM_000994.2 Homo 4.1E−240 sapiens ribosomal protein L32(RPL32), mRNA 3209 M00001437B:B08 MA16:G04 AF095287gi|3766235|gb|AF095287.1AF095287 2.5E−294 Homo sapiens pituitary tumortransforming gene protein 1 (PTTG1) mRNA, complete cds 3210M00001467B:H05 J04456 gi|187109|gb|J04456.1HUMLEC Human 1.9E−273 14 kdlectin mRNA, complete cds 3211 M00001468A:D02 MA16:F10 U71213gi|1621431|gb|U71213.1HSMIGST04 5.7E−127 Homo sapiens microsomalglutathione s- transferase gene, exon 4, alternatively splicedtranscripts, 3212 M00007131B:B11 MA243:B04 BC017931gi|17389843|gb|BC017931.1BC017931 0 Homo sapiens, Similar to RIKEN cDNA1110055A02 gene, clone MGC: 23962 IMAGE: 4669658, mRNA, complet 3213M00006650A:A10 MA241:E04 3214 M00006653C:B09 MA241:G04 0.0956 M17885gi|190231|gb|M17885.1HUMPPARP0 2.6E−186 Human acidic ribosomalphosphoprotein P0 mRNA, complete cds 3215 M00007154B:H08 MA243:G04BC016367 gi|16741029|gb|BC016367.1BC016367   1E−300 Homo sapiens,retinal short-chain dehydrogenase/reductase retSDR2, clone MGC: 24582IMAGE: 4133318, 3216 M00006740A:E02 MA241:A10 3217 M00021621A:D04MA243:A10 NM_003137 gi|15834623|ref|NM_003137.2 Homo 2.3E−285 sapiensSFRS protein kinase 1 (SRPK1), mRNA 3218 M00006740B:F11 MA241:B10AK022929 gi|10434601|dbj|AK022929.1AK022929 4.9E−277 Homo sapiens cDNAFLJ12867 fis, clone NT2RP2003702, highly similar to Homo sapiens 17beta-hydro 3219 M00006741C:A01 MA241:C10 AF201939gi|9295181|gb|AF201939.1AF201939 7.6E−183 Homo sapiens DC5 (DC5) mRNA,complete cds 3220 M00022171C:A04 MA243:F10 BC000793gb|12653990|gb|BC000793.1BC000793 0 Homo sapiens, eukaryotic translationinitiation factor 1A, clone MGC: 5131 IMAGE: 3451631, mRNA, co 3221M00026937C:B08 MA40:E05 AF151534 gi|8099341|gb|AF151534.1AF1515349.5E−177 Homo sapiens core histone macroH2A2.2 (MACROH2A2) mRNA,complete cds 3222 M00023367A:H06 MA37:G05 0.04244 BC015958gi|16358989|gb|BC015958.1BC015958 2.6E−257 Homo sapiens, clone MGC:15290 IMAGE: 3940309, mRNA, complete cds 3223 M00026985C:E12 MA40:F11BC000927 gi|12654216|gb|BC000927.1BC000927 0 Homo sapiens, Similar topoly (A) polymerase, clone MGC: 5378 IMAGE: 3445706, mRNA, complete cds3224 M00008100A:A07 MA31:B05 AF247820 gi|13186200|gb|AF247820.3AF2478204.1E−237 Homo sapiens NAG22 protein mRNA, complete cds 3225M00007936B:H07 MA27:E05 BC001929 gi|12804952|gb|BC001929.1BC0019298.4E−145 Homo sapiens, clone MGC: 3993 IMAGE: 2819500, mRNA, completecds 3226 M00008100C:E05 MA31:F05 0.05241 AF395203gi|15028449|gb|AF395203.1AF395203 6.5E−156 Cercopithecus aethiopsDnaJ-like protein (dj2) mRNA, complete cds 3227 M00007947B:B02 MA27:E113228 M00004105A:C09 MA25:F05 BC010042 gi|14603152|gb|BC010042.1BC0100421.6E−202 Homo sapiens, clone MGC: 19606 IMAGE: 3629513, mRNA, completecds 3229 M00001433C:D09 MA23:G05 U23070 gi|1262172|gb|U23070.1HSU23070 0Human putative transmembrane protein (nma) mRNA, complete cds 3230M00008027B:D09 MA29:B09 M33132 gi|189423|gb|M33132.1HUMP12AA 4.8E−165Human proliferating cell nucleolar protein P120 gene, exons 1-15 3231M00008028D:B01 MA29:D09 AB014595 gi|3327203|dbj|AB014595.1AB014595  1E−300 Homo sapiens mRNA for KIAA0695 protein, complete cds 3232M00008039A:C09 MA29:F09 0.04 BC013869 gi|17105403|gb|BC013869.1BC0138692.6E−291 Homo sapiens, clone IMAGE: 3831740, mRNA 3233 M00026905A:A10MA39:A11 AF069073 gi|3202003|gb|AF069073.1AF069073 0 Homo sapiens P8protein mRNA, complete cds 3234 M00026905D:C05 MA39:C11 BC010631gi|14714946|gb|BC010631.1BC010631 3.3E−281 Homo sapiens, clone IMAGE:3867552, mRNA 3235 M00001401B:A06 MA15:G05 U90313gi|2393721|gb|U90313.1HSU90313 0 Human glutathione-S-transferase homologmRNA, complete cds 3236 M00001402A:A08 MA15:H05 0.03584 X74215gi|414045|emb|X74215.1HSLON   7E−181 H. sapiens mRNA for Lonprotease-like protein 3237 M00005534C:E12 MA242:A05 0.55385 3238M00005542A:D09 MA242:D05 NM_001428 gi|16507965|ref|NM_001428.2 Homo1.1E−218 sapiens enolase 1, (alpha) (ENO1), mRNA 3239 M00007031D:E02MA240:F11 NM_005463 gi|14110410|ref|NM_005463.2 Homo 2.8E−186 sapiensheterogeneous nuclear ribonucleoprotein D-like (HNRPDL), transcriptvariant 1, mRNA 3240 M00007032A:D04 MA240:G11 D89678gi|3218539|dbj|D89678.1D89678 Homo 5.2E−225 sapiens mRNA for A+U-richelement RNA binding factor, complete cds 3241 M00005813C:F12 MA242:H11BC000659 gi|12653746|gb|BC000659.1BC000659 1.8E−245 Homo sapiens, cloneMGC: 1004 IMAGE: 3347423, mRNA, complete cds 3242 SL163 MA248:B050.82548 3243 SL164 MA248:C05 0.43491 AF415175gi|16589063|gb|AF415175.1AF415175 4.9E−102 Homo sapiens putative SH3domain- containing guanine exchange factor SGEF (SGEF) mRNA, complete cd3244 SL167 MA248:F05 0.13452 AK025140 gi|10437598|dbj|AK025140.1AK0251405.5E−159 Homo sapiens cDNA: FLJ21487 fis, clone COL05419 3245 SL168MA248:G05 0.72115 3246 SL169 MA248:H05 3247 M00023320B:A03 MA36:H11BC006428 gi|13623618|gb|BC006428.1BC006428 6.8E−298 Homo sapiens,hypothetical protein, clone MGC: 12969 IMAGE: 3343683, mRNA, completecds 3248 M00005350B:F10 MA246:C05 BC014191gi|15559670|gb|BC014191.1BC014191 4.7E−218 Homo sapiens, clone MGC:20633 IMAGE: 4761663, mRNA, complete cds 3249 M00008069D:F01 MA30:B050.09317 3250 M00022165B:C08 MA35:B05 BC012585gi|15214891|gb|BC012585.1BC012585 5.4E−199 Homo sapiens, clone IMAGE:4332982, mRNA 3251 M00022165C:E12 MA35:D05 NM_001024gi|14670385|ref|NM_001024.2 Homo   4E−184 sapiens ribosomal protein S21(RPS21), mRNA 3252 M00022166C:E07 MA35:E05 D87717gi|1663709|dbj|D87717.1D87717 Human 1.8E−139 mRNA for KIAA0013 gene,complete cds 3253 M00008072D:E12 MA30:F05 BC007581gi|14043186|gb|BC007581.1BC007581 6.5E−264 Homo sapiens, aldehydedehydrogenase 4 family, member A1, clone MGC: 15564 IMAGE: 3139944,mRNA, co 3254 M00022211B:D05 MA35:A11 AK025494gi|10438028|dbj|AK025494.1AK025494 2.3E−226 Homo sapiens cDNA: FLJ21841fis, clone HEP01831 3255 M00008089A:E09 MA30:G11 AB050577gi|14317901|dbj|AB050577.1AB050577 1.1E−231 Homo sapiens NUF2 mRNA forkinetochore protein Nuf2, complete cds 3256 M00003974D:E04 MA24:C11AF136185 gi|6625654|gb|AF136185.1AF136185 3.5E−228 Homo sapiens collagentype XVII (COL17A1) gene, 3′ UTR, long form 3257 M00003980D:F10 MA24:F11AF150100 gi|5107187|gb|AF150100.1AF150100   5E−252 Homo sapiens smallzinc finger-like protein (TIM9a) mRNA, complete cds 3258 M00003984D:C08MA24:H11 AL133560 gi|6599130|emb|AL133560.1HSM801406 0 Homo sapiensmRNA; cDNA DKFZp434M1414 (from clone DKFZp434M1414); partial cds 3259M00023373D:A01 MA22:E05 AK023875 gi|10435944|dbj|AK023875.1AK0238752.2E−201 Homo sapiens cDNA FLJ13813 fis, clone THYRO1000358, moderatelysimilar to SELENIUM-BINDING LIVER 3260 M00023396D:D01 MA22:H05 0.480263261 M00001437D:E12 MA16:A05 M30684 gi|177064|gb|M30684.1GORMHCBAA2.3E−260 Gorilla gorilla beta-2-microglobulin mRNA (GOGOB2M) 3262M00001438A:B09 MA16:B05 BC005230 gi|13528857|gb|BC005230.1BC0052303.6E−259 Homo sapiens, ubiquinol-cytochrome c reductase binding protein,clone MGC: 12253 IMAGE: 3961169, mR 3263 M00001369A:C07 MA14:E05AF097514 gi|4808600|gb|AF097514.1AF097514 2.2E−229 Homo sapiensstearoyl-CoA desaturase (SCD) mRNA, complete cds 3264 M00001439C:A07MA16:F05 BC017270 gi|16878126|gb|BC017270.1BC017270 3.7E−106 Homosapiens, homolog of yeast long chain polyunsaturated fatty acidelongation enzyme 2, clone M 3265 M00001369C:A05 MA14:H05 AF190167gi|6456117|gb|AF190167.1AF190167   1E−300 Homo sapiens membraneassociated protein SLP-2 (HUSLP2) mRNA, complete cds 3266 M00001468D:B11MA16:A11 BC008442 gi|14250074|gb|BC008442.1BC008442 5.3E−149 Homosapiens, Similar to transmembrane 4 superfamily member 1, clone MGC:14656 IMAGE: 4101110, mRN 3267 M00001386B:F08 MA14:B11 AF132818gi|6580834|gb|AF132818.1AF132818   3E−169 Homo sapiens colonKruppel-like factor (CKLF) mRNA, complete cds 3268 M00001387A:A08MA14:F11 NM_022551 gi|14165467|ref|NM_022551.2 Homo   7E−298 sapiensribosomal protein S18 (RPS18), mRNA 3269 M00007163A:B10 MA243:B05 D29013gi|517113|dbj|D29013.1HUMLNCAP 1.5E−178 Human mRNA for DNA polymerasebeta, complete cds 3270 M00006675C:A06 MA241:E05 BC009534gi|16306927|gb|BC009534.1BC009534 3.1E−250 Homo sapiens, clone IMAGE:3891886, mRNA, partial cds 3271 M00007191C:A06 MA243:G05 BC001765gi|12804678|gb|BC001765.1BC001765 1.7E−295 Homo sapiens, Similar tostromal antigen 2, clone MGC: 1282 IMAGE: 3352347, mRNA, complete cds3272 M00006678A:D02 MA241:H05 NM_002475 gi|17986280|ref|NM_002475.2 Homo  1E−240 sapiens myosin light chain 1 slow a (MLC1SA), mRNA 3273M00026941C:A12 MA40:E06 BC018910 gi|17511916|gb|BC018910.1BC0189102.6E−149 Homo sapiens, clone MGC: 10643 IMAGE: 3959973, mRNA, completecds 3274 M00026996A:E01 MA40:E12 0.05985 AF238079gi|7542489|gb|AF238079.1AF238079 0 Homo sapiens FK506 binding proteinprecursor (FKBP19) mRNA, complete cds 3275 M00023401B:E06 MA37:G120.71373 3276 M00027005B:D03 MA40:H12 AL137626gi|6808422|emb|AL137626.1HSM802390 5.8E−289 Homo sapiens mRNA; cDNADKFZp434O0712 (from clone DKFZp434O0712); partial cds 3277M00007937B:A02 MA27:C06 Z18948 gi|396712|emb|Z18948.1HSS100E 1.3E−174 H.sapiens mRNA for S100E calcium binding protein 3278 M00021612C:E11MA31:C06 0.60788 AB032969 gi|6329965|dbj|AB032969.1AB032969 1.2E−92 Homosapiens mRNA for KIAA1143 protein, partial cds 3279 M00007938C:C12MA27:G06 BC002360 gi|12803112|gb|BC002360.1BC002360 3.1E−122 Homosapiens, U5 snRNP-specific protein, 116 kD, clone MGC: 8581 IMAGE:2960986, mRNA, complete cds 3280 M00001623C:A06 MA23:F12 BC000629gi|12653688|gb|BC000629.1BC000629 9.9E−238 Homo sapiens, Similar toaspartyl-tRNA synthetase, clone MGC: 1562 IMAGE: 3344322, mRNA, completec 3281 M00001630D:A11 MA23:G12 AF179626 gi|6457296|gb|AF179626.1AF1796261.7E−298 Expression vector pGP100, complete sequence 3282 M00008044B:E11MA29:A11 AF083420 gi|5326765|gb|AF083420.1AF083420 4.5E−268 Homo sapiensbrain-specific STE20-like protein kinase 3 (STK3) mRNA, complete cds3283 M00008044C:C10 MA29:B11 AF224759 gi|12043739|gb|AF224759.1AF2247591.3E−277 Homo sapiens adenocarcinoma antigen ART1/P17 mRNA, complete cds3284 M00008044D:B08 MA29:C11 0.82704 BC019356gi|17939588|gb|BC019356.1BC019356 5.4E−27 Homo sapiens, clone IMAGE:3503646, mRNA 3285 M00008044D:C05 MA29:D11 M23161gi|339899|gb|M23161.1HUMTRANSC 5.4E−160 Human transposon-like elementmRNA 3286 M00022074C:A04 MA33:E11 3287 M00026910C:D12 MA39:E12 J03037gi|179771|gb|J03037.1HUMCAIIA Human 2.4E−263 carbonic anhydrase II mRNA,complete cds 3288 M00026913A:D06 MA39:G12 AK058163gi|16554226|dbj|AK058163.1AK058163 2.9E−275 Homo sapiens cDNA FLJ25434fis, clone TST06728, highly similar to ELONGATION FACTOR 1-ALPHA 1 3289M00001402C:H08 MA15:D06 BC000461 gi|12653382|gb|BC000461.1BC000461 0Homo sapiens, eukaryotic translation initiation factor 2, subunit 2(beta, 38 kD), clone MGC: 8508 3290 M00001404C:C11 MA15:F06 BC001497gi|16306642|gb|BC001497.1BC001497 1.4E−286 Homo sapiens, clone MGC: 2068IMAGE: 2823581, mRNA, complete cds 3291 M00005587B:G05 MA242:C06BC001566 gi|16306756|gb|BC001566.1BC001566 8.5E−282 Homo sapiens, cloneIMAGE: 3451980, mRNA, partial cds 3292 M00006934D:D10 MA240:C06 D63861gi|1769811|dbj|D63861.1D63861 Homo 7.5E−142 sapiens DNA for cyclophilin40, complete cds 3293 SL176 MA248:G06 3294 M00023295D:E05 MA36:A06M16957 gi|188249|gb|M16957.1HUMMHDRA2D 5.2E−227 Human MHC class IIHLA-DR2 (Dw2) b- associated glycoprotein beta-chain mRNA, 3′ end 3295M00023320B:C02 MA36:A12 3296 M00005401B:F12 MA246:B12 U47742gi|1517913|gb|U47742.1HSU47742 4.4E−54 Human monocytic leukaemia zincfinger protein (MOZ) mRNA, complete cds 3297 M00008074D:C05 MA30:F06AF035289 gi|2661043|gb|AF035289.1AF035289 3.3E−197 Homo sapiens clone23969 mRNA sequence 3298 M00022175B:F06 MA35:G06 U81002gi|4580010|gb|U81002.1HSU81002 Homo 1.1E−212 sapiens TRAF4 associatedfactor 1 mRNA, partial cds 3299 M00022230B:C10 MA35:G12 BC019061gi|17512149|gb|BC019061.1BC019061 7.5E−149 Homo sapiens, Similar toRIKEN cDNA 1500019E20 gene, clone IMAGE: 5089739, mRNA 3300M00022093C:C08 MA34:C06 AB061831 gi|17932955|dbj|AB061831.1AB0618311.1E−184 Homo sapiens RPL32 gene for ribosomal protein L32, complete cdsand sequence 3301 M00022093C:C12 MA34:D06 BC009401gi|14424786|gb|BC009401.1BC009401 9.9E−294 Homo sapiens, natural killercell transcript 4, clone MGC: 15353 IMAGE: 4300407, mRNA, complete cds3302 M00022132A:H07 MA34:F12 BC015557 gi|15990394|gb|BC015557.1BC015557  1E−300 Homo sapiens, clone MGC: 1567 IMAGE: 3050731, mRNA, completecds 3303 M00023397B:D04 MA22:A06 AF083441gi|5813822|gb|AF083441.1AF083441   1E−300 Homo sapiens SUI1 isolog mRNA,complete cds 3304 M00023399D:G04 MA22:E06 BC004450gi|13325265|gb|BC004450.1BC004450   1E−300 Homo sapiens, hypotheticalprotein MGC2650, clone MGC: 4188 IMAGE: 2820830, mRNA, complete cds 3305M00001439D:C09 MA16:A06 BC002446 gi|12803262|gb|BC002446.1BC002446 0Homo sapiens, MRJ gene for a member of the DNAJ protein family, cloneMGC: 1152 IMAGE: 3346070, mRN 3306 M00001441A:A09 MA16:B06 M57710gi|179530|gb|M57710.1HUMBPIGE 1.7E−295 Human IgE-binding protein(epsilon-BP) mRNA, complete cds 3307 M00001369D:E02 MA14:C06 AF034546gi|3127052|gb|AF034546.1AF034546 1.9E−195 Homo sapiens sorting nexin 3(SNX3) mRNA, complete cds 3308 M00001371D:H10 MA14:E06 3309M00001372A:D01 MA14:F06 AF151872 gi|4929696|gb|AF151872.1AF151872 0 Homosapiens CGI-114 protein mRNA, complete cds 3310 M00001444C:F03 MA16:G06AL359678 gi|15215911|emb|AL359678.15AL359678 0 Human DNA sequence fromclone RP11- 550J21 on chromosome 9, complete sequence [Homo sapiens]3311 M00001445A:B02 BC003401 gi|13097293|gb|BC003401.1BC003401 9.7E−291Homo sapiens, ribosomal protein S14, clone MGC: 5429 IMAGE: 3448752,mRNA, complete cds 3312 M00001388D:F11 MA14:D12 BC002609gi|12803554|gb|BC002609.1BC002609 0 Homo sapiens, chromobox homolog 1(Drosophila HP1 beta), clone MGC: 1267 IMAGE: 3140815, mRNA, comp 3313M00001481C:A12 MA16:F12 AB033007 gi|6330242|dbj|AB033007.1AB0330072.9E−88 Homo sapiens mRNA for KIAA1181 protein, partial cds 3314M00001389B:B05 MA14:G12 BC013858 gi|15426627|gb|BC013858.1BC013858  2E−239 Homo sapiens, clone IMAGE: 3869909, mRNA 3315 M00001389C:G01MA14:H12 0.07529 AY004872 gi|9508996|gb|AY004872.1 Homo sapiens 4.6E−175thioredoxin (TXN) mRNA, complete cds 3316 M00001482D:D11 MA16:H120.07738 BC009982 gi|14602997|gb|BC009982.1BC009982 5.1E−169 Homosapiens, clone IMAGE: 4121355, mRNA, partial cds 3317 M00006809B:F04MA241:D12 0.62333 3318 I:3325119:07A01:A01 MA127:A01 U21936gi|717118|gb|U21936.1HSU21936 Human 1.4E−149 peptide transporter(HPEPT1) mRNA, complete cds 3319 I:3033345:07A01:C01 MA127:C01 BC004982gi|13436412|gb|BC004982.1BC004982   9E−229 Homo sapiens, glucosephosphate isomerase, clone MGC: 3935 IMAGE: 2906270, mRNA, complete cds3320 I:3176222:07A01:E07 MA127:E07 U09413 gi|488554|gb|U09413.1HSU09413Human 1.9E−264 zinc finger protein ZNF135 mRNA, complete cds 3321I:2510627:07B01:G07 MA129:G07 BC002803 gi|12803912|gb|BC002803.1BC002803  1E−300 Homo sapiens, hypothetical protein, clone MGC: 3402 IMAGE:3636703, mRNA, complete cds 3322 I:1705208:06B01:A01 MA125:A01 X52541gi|31129|emb|X52541.1HSEGR1 Human 0 mRNA for early growth responseprotein 1 (hEGR1) 3323 I:1672781:06B01:C07 MA125:C07 BC010042gi|14603152|gb|BC010042.1BC010042   1E−300 Homo sapiens, clone MGC:19606 IMAGE: 3629513, mRNA, complete cds 3324 I:1712888:06B01:D07MA125:D07 AL137469 gi|6808076|emb|AL137469.1HSM802187   1E−300 Homosapiens mRNA; cDNA DKFZp434P2422 (from clone DKFZp434P2422); partial cds3325 I:1696224:06B01:E07 MA125:E07 NM_005346 gi|5579470|ref|NM_005346.2Homo   1E−300 sapiens heat shock 70 kD protein 1B (HSPA1B), mRNA 3326I:3935034:06B01:H07 MA125:H07 BC007616 gi|14043251|gb|BC007616.1BC0076161.2E−249 Homo sapiens, clone MGC: 15728 IMAGE: 3354330, mRNA, completecds 3327 I:1800114:03A01:E01 MA111:E01 M24559gi|514365|gb|M24559.1HUMIGRPOLY 1.5E−205 Human poly-Ig receptortransmembrane secretory component mRNA, 3′ end 3328 I:1976029:03A01:D07MA111:D07 BC000629 gi|12653688|gb|BC000629.1BC000629 1.1E−299 Homosapiens, Similar to aspartyl-tRNA synthetase, clone MGC: 1562 IMAGE:3344322, mRNA, complete c 3329 I:1439934:03B01:E07 MA113:E07 0.17464M64788 gi|190855|gb|M64788.1HUMRAP1GAP 5.9E−184 Human GTPase activatingprotein (rap1GAP) mRNA, complete cds 3330 I:2512879:01A01:C01 MA103:C01M12271 gi|178091|gb|M12271.1HUMADH1CB 3.7E−290 Homo sapiens class Ialcohol dehydrogenase (ADH1) alpha subunit mRNA, complete cds 3331I:2900277:01B01:B07 MA105:B07 BC015492 gi|15930098|gb|BC015492.1BC015492  1E−300 Homo sapiens, clone MGC: 8967 IMAGE: 3915505, mRNA, completecds 3332 I:1479255:01A01:C07 MA103:C07 NM_002245gi|15451900|ref|NM_002245.2 Homo   1E−300 sapiens potassium channel,subfamily K, member 1 (TWIK-1) (KCNK1), mRNA 3333 I:2648612:04B01:A01MA117:A01 NM_006013 gi|15718685|ref|NM_006013.2 Homo   1E−300 sapiensribosomal protein L10 (RPL10), mRNA 3334 I:1889867:04A01:C01 MA115:C01AF004563 gi|3041874|gb|AF004563.1AF004563 8.2E−148 Homo sapiens hUNC18balternatively- spliced mRNA, complete cds 3335 I:1858905:04A01:D01MA115:D01 BC015520 gi|15930171|gb|BC015520.1BC015520 1.8E−211 Homosapiens, ribonuclease, RNase A family, 4, clone MGC: 9306 IMAGE:3905439, mRNA, complete cds 3336 I:2591494:04B01:H01 MA117:H01 BC009084gi|14290606|gb|BC009084.1BC009084 0 Homo sapiens, Similar to seleniumbinding protein 1, clone MGC: 9270 IMAGE: 3853674, mRNA, complete 3337I:2916261:04B01:A07 MA117:A07 BC016855 gi|16877177|gb|BC016855.1BC0168555.9E−289 Homo sapiens, clone MGC: 17066 IMAGE: 3850361, mRNA, completecds 3338 I:2397815:04B01:B07 MA117:B07 BC007888gi|14043894|gb|BC007888.1BC007888 3.3E−253 Homo sapiens, eukaryotictranslation initiation factor 2, subunit 2 (beta, 38 kD), clone MGC:1417 3339 I:2182095:04B01:D07 MA117:D07 NM_002580gi|4505604|ref|NM_002580.1 Homo 5.8E−289 sapiens pancreatitis-associatedprotein (PAP), mRNA 3340 I:2506194:02A01:A01 MA107:A01 U36601gi|1036798|gb|U36601.1HSU36601 Homo 1.3E−240 sapiens heparanN-deacetylase/N- sulfotransferase-2 mRNA, complete cds 3341I:1806219:02A01:C01 MA107:C01 U34279 gi|1236798|gb|U34279.1HSU342795.4E−202 Human uroguanylin mRNA, complete cds 3342 I:1729724:02A01:G07MA107:G07 NM_002487 gi|10800414|ref|NM_002487.2 Homo 3.1E−169 sapiensnecdin homolog (mouse) (NDN), mRNA 3343 I:1886842:05A02:G01 MA120:G01BC010578 gi|14714852|gb|BC010578.1BC010578 1.5E−292 Homo sapiens, cloneMGC: 9344 IMAGE: 3458845, mRNA, complete cds 3344 I:1352669:05A02:B07MA120:B07 0.10093 BC016752 gi|16876952|gb|BC016752.1BC016752 1.4E−169Homo sapiens, clone IMAGE: 2959721, mRNA 3345 I:1755847:05B02:C07MA122:C07 U51095 gi|1777771|gb|U51095.1HSU51095 5.9E−230 Human homeoboxprotein Cdx1 mRNA, complete cds 3346 I:1803418:05B02:D07 MA122:D07BC006168 gi|13544071|gb|BC006168.1BC006168 0 Homo sapiens, clone IMAGE:3960207, mRNA, partial cds 3347 I:1568725:05B02:F07 MA122:F07 0.36394D49410 gi|684968|dbj|D49410.1HUMIL3RA12 7.7E−187 Homo sapiens gene forinterleukin 3 receptor alpha subunit, exon 12 and partial cds 3348I:1857708:05A02:G07 MA120:G07 U43381 gi|1155348|gb|U43381.1HSU433811.3E−283 Human Down Syndrome region of chromosome 21 DNA 3349I:1687060:05B02:G07 MA122:G07 U57645 gi|1816511|gb|U57645.1HSU576453.3E−281 Human helix-loop-helix proteins Id-1 (ID- 1) and Id-1′ (ID-1)genes, complete cds 3350 I:3407289:07A02:A07 MA128:A07 0.21116 AB011135gi|3043649|dbj|AB011135.1AB011135 1.7E−68 Homo sapiens mRNA for KIAA0563protein, complete cds 3351 I:1235535:07A02:B07 MA128:B07 NM_001012gi|4506742|ref|NM_001012.1 Homo 3.8E−156 sapiens ribosomal protein S8(RPS8), mRNA 3352 I:1525795:03B02:D07 MA114:D07 X05360gi|29838|emb|X05360.1HSCDC2 Human 1.5E−289 CDC2 gene involved in cellcycle control 3353 I:3744592:03A02:H07 MA112:H07 S76992gi|913345|gb|S76992.1S76992   1E−194 VAV2 = VAV oncogene homolog [human,fetal brain, mRNA Partial, 2753 nt] 3354 I:1485817:01A02:B01 MA104:B01L14787 gi|292930|gb|L14787.1HUMZFPA Human 3.4E−247 DNA-binding proteinmRNA, 3′end 3355 I:2365149:01B02:B01 MA106:B01 U58917gi|2826475|gb|U58917.1HSU58917 Homo   9E−208 sapiens IL-17 receptormRNA, complete cds 3356 I:1439677:01A02:D01 MA104:D01 AL096780gi|5420184|emb|AL096780.1HS384D86A 1.8E−146 Novel human gene mapping tochomosome 22p13.33 similar to mouse Choline/Ethanolamine Kinase (O553357 I:2372275:01B02:G01 MA106:G01 BC019252gi|17939418|gb|BC019252.1BC019252   1E−300 Homo sapiens, clone MGC: 1111IMAGE: 3503549, mRNA, complete cds 3358 I:3211615:01B02:H01 MA106:H01BC013808 gi|15489437|gb|BC013808.1BC013808   2E−230 Homo sapiens, TATAbox binding protein (TBP)-associated factor, RNA polymerase I, A, 48 kD,clone 3359 I:2368282:01B02:B07 MA106:B07 AK056794gi|16552300|dbj|AK056794.1AK056794 5.8E−209 Homo sapiens cDNA FLJ32232fis, clone PLACE6004578, highly similar to CYTOCHROME P450 11A1, MITO3360 I:1737833:04A02:D01 MA116:D01 D26598 gi|565646|dbj|D26598.1HUMPSH1  1E−300 Human mRNA for proteasome subunit HsC10-II, complete cds 3361I:2382192:04B02:F01 MA118:F01 Y12653 gi|2546963|emb|Y12653.1HSDIUBIQU1.6E−264 H. sapiens mRNA for diubiquitin 3362 I:1958902:04A02:D07MA116:D07 D87258 gi|1513058|dbj|D87258.1D87258 Homo 0 sapiens mRNA forserin protease with IGF-binding motif, complete cds 3363I:1704472:04B02:G07 MA118:G07 U66871 gi|1519518|gb|U66871.1HSU66871  7E−161 Human enhancer of rudimentary homolog mRNA, complete cds 3364I:1903767:04A02:H07 MA116:H07 AF025304 gi|2739055|gb|AF025304.1AF025304  1E−300 Homo sapiens protein-tyrosine kinase EPHB2v (EPHB2) mRNA,complete cds 3365 I:1268080:02A02:C01 MA108:C01 AB006631gi|14133200|dbj|AB006631.2AB006631 0 Homo sapiens mRNA for KIAA0293gene, partial cds 3366 I:1347384:02A02:C07 MA108:C07 U78579gi|1743878|gb|U78579.1HSU78579 0 Human type I phosphatidylinositol-4-phosphate 5-kinase beta (STM7) mRNA, partial cds 3367I:2344817:08B01:H02 MA133:H02 3368 I:3236109:08A01:B08 MA131:B08 0.464413369 I:2832506:07A01:H08 MA127:H08 BC000851gi|12654082|gb|BC000851.1BC000851 8.5E−282 Homo sapiens, ribosomalprotein L13, clone IMAGE: 3458439, mRNA 3370 I:1673876:06B01:B02MA125:B02 V00568 gi|34815|emb|V00568.1HSMYC1 Human   1E−300 mRNAencoding the c-myc oncogene 3371 I:3686211:06B01:E02 MA125:E02 X59960gi|402620|emb|X59960.1HSSPMYEL   1E−300 H. sapiens mRNA forsphingomyelinase 3372 I:2449837:06B01:H02 MA125:H02 BC000070gi|12652644|gb|BC000070.1BC000070   3E−219 Homo sapiens, small nuclearribonucleoprotein polypeptide G, clone MGC: 1614 IMAGE: 3503973, mRNA,3373 I:1613874:06B01:C08 MA125:C08 AF019952gi|2655036|gb|AF019952.1AF019952 0 Homo sapiens tumor suppressing STFcDNA 1 (TSSC1) mRNA, complete cds 3374 I:1813409:03A01:C02 MA111:C02BC009244 gi|14328061|gb|BC009244.1BC009244   1E−300 Homo sapiens,isocitrate dehydrogenase 2 (NADP+), mitochondrial, clone MGC: 3700IMAGE: 2959540, mR 3375 I:1975514:03A01:A08 MA111:A08 S52873gi|263656|gb|S52873.1S52873 cytidine 5.7E−286 deaminase [human,monocytoid cell line U937, mRNA Partial, 736 nt] 3376I:1403294:01A01:B02 MA103:B02 0.13199 3377 I:2414624:01B01:D02 MA105:D02U31278 gi|950198|gb|U31278.1HSU31278 Homo 0 sapiens mitotic feedbackcontrol protein Madp2 homolog mRNA, complete cds 3378I:2901811:01B01:H02 MA105:H02 BC013081 gi|15341817|gb|BC013081.1BC0130812.6E−213 Homo sapiens, Similar to metallothionein 3 (growth inhibitoryfactor (neurotrophic)), clone MGC: 1 3379 I:2683564:01B01:B08 MA105:B08V00522 gi|32122|emb|V00522.1HSHL01 Human 2.5E−294 mRNA encoding majorhistocompatibility complex gene HLA-DR beta-I 3380 I:2725511:01B01:C08MA105:C08 AF004849 gi|2627330|gb|AF004849.1AF004849 1.4E−177 Homosapiens PKY protein kinase mRNA, complete cds 3381 I:1431273:04A01:A02MA115:A02 M82962 gi|535474|gb|M82962.1HUMPPH Human   1E−268N-benzoyl-L-tyrosyl-p-amino-benzoic acid hydrolase alpha subunit (PPHalpha) mRNA, complete cds 3382 I:1636639:04B01:A02 MA117:A02 AF055009gi|3005731|gb|AF055009.1AF055009 0 Homo sapiens clone 24747 mRNAsequence 3383 I:2455617:04B01:D02 MA117:D02 BC008281gi|14249818|gb|BC008281.1BC008281 3.2E−281 Homo sapiens, guanosinemonophosphate reductase, clone MGC: 10464 IMAGE: 3635871, mRNA, completecd 3384 I:2952504:04B01:F02 MA117:F02 U72849gi|4097996|gb|U72849.1HSAPEVPL7   1E−300 Homo sapiens envoplakin (EVPL)gene, exon 22 and complete cds 3385 I:1483847:04A01:A08 MA115:A08AF026293 gi|2559011|gb|AF026293.1AF026293   4E−93 Homo sapienschaperonin containing t- complex polypeptide 1, beta subunit (Cctb)mRNA, complete cds 3386 I:2923150:04B01:B08 MA117:B08 M18963gi|190978|gb|M18963.1HUMREGA 1.2E−237 Human islet of Langerhansregenerating protein (reg) mRNA, complete cds 3387 I:1813133:04A01:F08MA115:F08 X12597 gi|32326|emb|X12597.1HSHMG1 Human 1.3E−255 mRNA forhigh mobility group-1 protein (HMG-1) 3388 I:2510171:04B01:H08 MA117:H080.15344 X04503 gi|36490|emb|X04503.1HSSLIPR Human 1.1E−259 SLPI mRNAfragment for secretory leucocyte protease inhibitor 3389I:2190284:02A01:H02 MA107:H02 D84107 gi|1669546|dbj|D84107.1D84107 Homo0 sapiens mRNA for RBP-MS/type 1, complete cds 3390 I:1522716:05B02:B02MA122:B02 X56134 gi|37849|emb|X56134.1HSVIMENT 0 Human mRNA for vimentin3391 I:1901271:05A02:G02 MA120:G02 U90916 gi|1913897|gb|U90916.1HSU90916  9E−288 Human clone 23815 mRNA sequence 3392 I:1820522:05B02:H02MA122:H02 BC002806 gi|12803918|gb|BC002806.1BC002806 1.1E−299 Homosapiens, phosphatidic acid phosphatase type 2C, clone MGC: 3813 IMAGE:3659728, mRNA, complete 3393 I:2365295:05A02:A08 MA120:A08 BC015460gi|15930032|gb|BC015460.1BC015460 3.8E−26 Homo sapiens, Similar toglutaminyl- peptide cyclotransferase (glutaminyl cyclase), clone IMAGE:39 3394 I:1335140:05A02:C08 MA120:C08 X02152gi|34312|emb|X02152.1HSLDHAR 0 Human mRNA for lactate dehydrogenase- A(LDH-A, EC 1.1.1.27) 3395 I:1822577:05B02:D08 MA122:D08 BC001941gi|12804976|gb|BC001941.1BC001941 1.7E−270 Homo sapiens, tissue specifictransplantation antigen P35B, clone MGC: 4302 IMAGE: 2819332, mRNA, c3396 I:1306814:06B02:A08 MA126:A08 AK026649gi|10439547|dbj|AK026649.1AK026649 9.8E−135 Homo sapiens cDNA: FLJ22996fis, clone KAT11938 3397 I:3034694:06B02:D08 MA126:D08 BC008935gi|14286273|gb|BC008935.1BC008935 4.6E−299 Homo sapiens, Similar tosolute carrier family 25 (mitochondrial carrier; adenine nucleotide tran3398 I:1453049:03B02:A02 MA114:A02 X76180 gi|452649|emb|X76180.1HSLASNA2.7E−269 H. sapiens mRNA for lung amiloride sensitive Na+ channelprotein 3399 I:1453748:03B02:D02 MA114:D02 BC013579gi|15488897|gb|BC013579.1BC013579 2.6E−135 Homo sapiens, Similar tocalpastatin, clone MGC: 9402 IMAGE: 3878564, mRNA, complete cds 3400I:3001492:03A02:G02 MA112:G02 X75042 gi|402648|emb|X75042.1HSRNAREL1.6E−295 H. sapiens rel proto-oncogene mRNA 3401 I:3876715:03A02:C08MA112:C08 BC000373 gi|12653210|gb|BC000373.1BC000373 6.4E−161 Homosapiens, Similar to amyloid beta (A4) precursor-like protein 2, cloneMGC: 8371 IMAGE: 2820109 3402 I:2992851:03A02:D08 MA112:D08 AF190637gi|10441643|gb|AF190637.1AF190637 1.5E−286 Homo sapiens nephrin mRNA,complete cds 3403 I:1500649:03B02:G08 MA114:G08 AB008430gi|2766164|dbj|AB008430.1AB008430   1E−234 Homo sapiens mRNA for CDEP,complete cds 3404 I:1512943:01A02:B02 MA104:B02 AJ005036gi|3059108|emb|AJ005036.1HSAJ5036 9.1E−288 Homo sapiens mRNA forphosphodiesterase 3A (from corpus cavernosum) 3405 I:1467565:01A02:D02MA104:D02 BC014991 gi|15929072|gb|BC014991.1BC014991 3.7E−262 Homosapiens, clone MGC: 23226 IMAGE: 4909112, mRNA, complete cds 3406I:2455118:01B02:D08 MA106:D08 X16396 gi|35070|emb|X16396.1HSNMTDC 0Human mRNA for NAD-dependent methylene tetrahydrofolate dehydrogenasecyclohydrolase (EC 1.5.1.15) 3407 I:2840251:01B02:E08 MA106:E08 U52513gi|1777781|gb|U52513.1HSU52513 0 Human RIG-G mRNA, complete cds 3408I:2911347:10B02:E02 MA67:E02 0.28302 3409 I:1812030:10B02:G08 MA67:G08AB049758 gi|10800085|dbj|AB049758.1AB049758 3.6E−200 Homo sapiens mawbpmRNA for MAWD binding protein, complete cds 3410 I:2663606:04B02:F08MA118:F08 U37690 gi|1017824|gb|U37690.1HSU37690 5.2E−196 Human RNApolymerase II subunit (hsRPB10) mRNA, complete cds 3411I:1308333:02A02:E02 MA108:E02 BC017338 gi|16878283|gb|BC017338.1BC0173381.4E−286 Homo sapiens, fucosidase, alpha-L-1, tissue, clone MGC: 29579IMAGE: 4871788, mRNA, complete cds 3412 I:1578941:02B02:E02 MA110:E02AK058013 gi|16554011|dbj|AK058013.1AK058013 1.2E−246 Homo sapiens cDNAFLJ25284 fis, clone STM06787, highly similar to 15- HYDROXYPROSTAGLANDINDEHYDR 3413 I:1535439:02A02:D08 MA108:D08 M83363gi|190096|gb|M83363.1HUMPMCA 3.1E−250 Human plasma membrane calcium-pumping ATPase (PMCA4) mRNA, complete cds 3414 I:1857475:02B02:H08MA110:H08 AF009203 gi|2454508|gb|AF009203.1AF009203 1.5E−292 Homosapiens YAC clone 377A1 unknown mRNA, 3′untranslated region 3415I:2908878:08B01:F09 MA133:F09 0.46085 3416 I:2830575:07A01:C03 MA127:C030.06365 D16431 gi|598955|dbj|D16431.1HUMHDGF 1.7E−289 Human mRNA forhepatoma-derived growth factor, complete cds 3417 I:1557906:07B01:G03MA129:G03 AK057477 gi|16553199|dbj|AK057477.1AK057477 5.8E−230 Homosapiens cDNA FLJ32915 fis, clone TESTI2006425 3418 I:2200604:06B01:F03MA125:F03 U47105 gi|4457236|gb|U47105.2HSU47105 Homo 0 sapiens H105e3(H105e3) mRNA, complete cds 3419 I:1653326:06A01:C09 MA123:C09 BC018881gi|17403014|gb|BC018881.1BC018881   1E−296 Homo sapiens, clone IMAGE:3617364, mRNA 3420 I:1720149:06A01:G09 MA123:G09 U48959gi|7239695|gb|U48959.2HSU48959 Homo 2.4E−291 sapiens myosin light chainkinase (MLCK) mRNA, complete cds 3421 I:1560987:03B01:G03 MA113:G03U17077 gi|1000711|gb|U17077.1HSU17077 2.3E−92 Human BENE mRNA, partialcds 3422 I:1510714:03B01:G09 MA113:G09 NM_000240gi|4557734|ref|NM_000240.1 Homo 6.3E−264 sapiens monoamine oxidase A(MAOA), nuclear gene encoding mitochondrial protein, mRNA 3423I:2501484:01B01:A03 MA105:A03 AB002438 gi|2943813|dbj|AB002438.1AB0024381.1E−268 Homo sapiens mRNA from chromosome 5q21-22, clone: FBR89 3424I:1379063:01A01:B03 MA103:B03 U28055 gi|1141776|gb|U28055.1HSU28055 Homo0 sapiens hepatocyte growth factor-like protein homolog mRNA, partialcds 3425 I:2797902:01B01:C03 MA105:C03 0.07692 BC019038gi|17512114|gb|BC019038.1BC019038 6.6E−289 Homo sapiens, small nuclearRNA activating complex, polypeptide 1, 43 kD, clone MGC: 20773 IMAGE: 453426 I:1805613:01B01:G03 MA105:G03 U79725 gi|1814276|gb|U79725.1HSU797255.4E−202 Human A33 antigen precursor mRNA, complete cds 3427I:1524885:01A01:H03 MA103:H03 Y12065 gi|2230877|emb|Y12065.1HSNOP56 0Homo sapiens mRNA for nucleolar protein hNop56 3428 I:2888464:01B01:H03MA105:H03 S73591 gi|688296|gb|S73591.1S73591 Homo 1.7E−267 sapiensbrain-expressed HHCPA78 homolog VDUP1 (Gene) mRNA, complete cds 3429I:1992788:04B01:B03 MA117:B03 AL161985gi|7328121|emb|AL161985.1HSM802609 0 Homo sapiens mRNA; cDNADKFZp761J1810 (from clone DKFZp761J1810) 3430 I:1413451:04A01:F03MA115:F03 D88648 gi|2653566|dbj|D88648.1D88648 Homo 4.1E−184 sapiensmRNA for B-FABP, complete cds 3431 I:2779515:04B01:C09 MA117:C09AL136543 gi|6807646|emb|AL136543.1HSM801517 2.2E−285 Homo sapiens mRNA;cDNA DKFZp761K0511 (from clone DKFZp761K0511); partial cds 3432I:1583076:02B01:G09 MA109:G09 NM_000669 gi|11496888|ref|NM_000669.2 Homo  6E−261 sapiens alcohol dehydrogenase 1C (class I), gamma polypeptide(ADH1C), mRNA 3433 I:3070110:05A02:B03 MA120:B03 AF061016gi|3127126|gb|AF061016.1AF061016 6.4E−295 Homo sapiens UDP-glucosedehydrogenase (UGDH) mRNA, complete cds 3434 I:1904493:05A02:H03MA120:H03 Z22555 gi|397606|emb|Z22555.1HSCLA1GNA 9.7E−229 H. sapiensencoding CLA-1 mRNA 3435 I:2860815:05A02:A09 MA120:A09 AF067420gi|3201899|gb|AF067420.1AF067420 1.7E−100 Homo sapiens SNC73 protein(SNC73) mRNA, complete cds 3436 I:1930135:07A02:G03 MA128:G03 3437I:3747901:06B02:G03 MA126:G03 BC004979 gi|13436403|gb|BC004979.1BC0049791.6E−289 Homo sapiens, clone MGC: 3855 IMAGE: 2905681, mRNA, completecds 3438 I:1720946:06A02:A09 MA124:A09 BC010733gi|14789594|gb|BC010733.1BC010733 1.1E−296 Homo sapiens, clone IMAGE:3897044, mRNA, partial cds 3439 I:2877413:06B02:D09 MA126:D09 BC000700gi|12653822|gb|BC000700.1BC000700 5.5E−255 Homo sapiens, clone MGC: 3101IMAGE: 3350198, mRNA, complete cds 3440 I:3035279:06B02:E09 MA126:E09BC001125 gi|12654578|gb|BC001125.1BC001125   2E−276 Homo sapiens,peptidylprolyl isomerase B (cyclophilin B), clone MGC: 2224 IMAGE:2966791, mRNA, com 3441 I:2503913:03A02:E09 MA112:E09 BC010952gi|15012094|gb|BC010952.1BC010952 1.5E−261 Homo sapiens, Similar toprotease inhibitor 3, skin-derived (SKALP), clone MGC: 13613 IMAGE:408315 3442 I:1517380:01A02:B03 MA104:B03 AB033032gi|6330486|dbj|AB033032.1AB033032 1.2E−277 Homo sapiens mRNA forKIAA1206 protein, partial cds 3443 I:3138128:01B02:C03 MA106:C03 D31887gi|505101|dbj|D31887.1HUMORFKG1P   1E−300 Human mRNA for KIAA0062 gene,partial cds 3444 I:2453722:01A02:E03 MA104:E03 BC003582gi|13097770|gb|BC003582.1BC003582   1E−300 Homo sapiens, polymerase(RNA) II (DNA directed) polypeptide F, clone MGC: 2669 IMAGE: 3546712,mRN 3445 I:1414260:01A02:A09 MA104:A09 AB002318gi|2224580|dbj|AB002318.1AB002318 3.4E−284 Human mRNA for KIAA0320 gene,partial cds 3446 I:2891247:01B02:A09 MA106:A09 D43638gi|940399|dbj|D43638.1HUMMTG8AP 8.4E−151 Human mRNA for MTG8a protein,complete cds 3447 I:1682176:01A02:F09 MA104:F09 U78556gi|1688306|gb|U78556.1HSU78556   1E−293 Human cisplatin resistanceassociated alpha protein (hCRA alpha) mRNA, complete cds 3448I:2739076:04A02:D03 MA116:D03 NM_001023 gi|14591915|ref|NM_001023.2 Homo2.1E−248 sapiens ribosomal protein S20 (RPS20), mRNA 3449I:1900378:04B02:F03 MA118:F03 AB002363 gi|2224670|dbj|AB002363.1AB0023633.1E−275 Human mRNA for KIAA0365 gene, partial cds 3450I:1603391:04A02:G03 MA116:G03 AF036874 gi|9738910|gb|AF036874.1AF0368743.7E−275 Homo sapiens multiple endocrine neoplasia type 1 candidateprotein number 18 (HSPF2) mRNA, complet 3451 I:2018222:04A02:C09MA116:C09 BC008795 gi|14250659|gb|BC008795.1BC008795   2E−192 Homosapiens, proteasome (prosome, macropain) subunit, beta type, 9 (largemultifunctional protea 3452 I:1327263:04A02:F09 MA116:F09 M25629gi|186652|gb|M25629.1HUMKALX 1.4E−283 Human kallikrein mRNA, completecds, clone clone phKK25 3453 I:1734393:02A02:B09 MA108:B09 X73502gi|406853|emb|X73502.1HSENCY20 H. Sapiens 0 mRNA for cytokeratin 20 3454I:2190607:02A02:E09 MA108:E09 BC008012 gi|14124971|gb|BC008012.1BC0080123.5E−244 Homo sapiens, eukaryotic translation elongation factor 1 delta(guanine nucleotide exchange prote 3455 I:2447969:08A01:E04 MA131:E040.16896 3456 I:1753033:08B01:H10 MA133:H10 AL359055gi|8518180|emb|AL359055.1IR2344436 9.6E−24 Homo sapiens mRNA full lengthinsert cDNA clone EUROIMAGE 2344436 3457 I:2456393:07B01:E10 MA129:E10BC005029 gi|13477142|gb|BC005029.1BC005029 3.6E−259 Homo sapiens,hypothetical protein FLJ10718, clone MGC: 12594 IMAGE: 4040181, mRNA,complete cds 3458 I:1719920:06B01:A04 MA125:A04 0.13978 BC001903gi|12804902|gb|BC001903.1BC001903 1.4E−274 Homo sapiens, Similar tointerleukin 10 receptor, beta, clone MGC: 2210 IMAGE: 3544611, mRNA,compl 3459 I:2927362:06B01:H04 MA125:H04 BC019336gi|17939560|gb|BC019336.1BC019336 0 Homo sapiens, clone IMAGE: 3617778,mRNA, partial cds 3460 I:4082816:06B01:F10 MA125:F10 BC001365gi|12655034|gb|BC001365.1BC001365 6.1E−230 Homo sapiens, ribosomalprotein L4, clone MGC: 2201 IMAGE: 3051487, mRNA, complete cds 3461I:1803446:03A01:A04 MA111:A04 BC000062 gi|12652632|gb|BC000062.1BC000062  1E−300 Homo sapiens, solute carrier family 1 (neutral amino acidtransporter), member 5, clone MGC: 1387 3462 I:1557490:03A01:C04MA111:C04 BC003560 gi|13097707|gb|BC003560.1BC003560 0 Homo sapiens,ribophorin II, clone MGC: 1817 IMAGE: 3546673, mRNA, complete cds 3463I:1445895:03B01:E10 MA113:E10 BC009196 gi|14327943|gb|BC009196.1BC0091963.6E−131 Homo sapiens, phosphatidic acid phosphatase type 2B, clone MGC:15306 IMAGE: 3960223, mRNA, complet 3464 I:1336836:01A01:H04 MA103:H04M32215 gi|307524|gb|M32215.1HUMTSHRX   1E−300 Human thyroid stimulatoryhormone receptor (TSHR) mRNA, complete cds 3465 I:1802745:01B01:E10MA105:E10 D42087 gi|576555|dbj|D42087.1HUMHA0793A 8.4E−279 Human mRNAfor KIAA0118 gene, partial cds 3466 I:2503003:01B01:H10 MA105:H10AF020352 gi|2655054|gb|AF020352.1AF020352 1.4E−255 Homo sapiens NADH:ubiquinone oxidoreductase 15 kDa IP subunit mRNA, nuclear gene encodingmitochon 3467 I:1655377:10A01:F04 MA64:F04 AK000706gi|7020960|dbj|AK000706.1AK000706 2.7E−210 Homo sapiens cDNA FLJ20699fis, clone KAIA2372 3468 I:1430662:04A01:A04 MA115:A04 AF078035gi|4322303|gb|AF078035.1AF078035 3.9E−262 Homo sapiens translationinitiation factor IF2 mRNA, complete cds 3469 I:3335055:04A01:G04MA115:G04 BC004390 gi|13325149|gb|BC004390.1BC004390 3.7E−181 Homosapiens, phosphatidylserine synthase 1, clone MGC: 10968 IMAGE: 3634879,mRNA, complete cds 3470 I:2457671:04B01:B10 MA117:B10 BC000469gi|12653398|gb|BC000469.1BC000469 4.3E−299 Homo sapiens, eukaryotictranslation initiation factor 3, subunit 7 (zeta, 66/67 kD), clone MGC:85 3471 I:1641421:02A01:C10 MA107:C10 S69369 gi|545844|gb|S69369.1S693691.5E−180 PAX3A = transcription factor [human, adult cerebellum, mRNA,1248 nt] 3472 I:1655225:02B01:E10 MA109:E10 AB002331gi|2224606|dbj|AB002331.1AB002331 7.1E−273 Human mRNA for KIAA0333 gene,partial cds 3473 I:1313325:05A02:B04 MA120:B04 U09550gi|1184036|gb|U09550.1HSU09550 5.2E−283 Human oviductal glycoproteinmRNA, complete cds 3474 I:1558081:05B02:A10 MA122:A10 NM_004530gi|11342665|ref|NM_004530.1 Homo 0 sapiens matrix metalloproteinase 2(gelatinase A, 72 kD gelatinase, 72 kD type IV collagenase) (MMP2 3475I:1889191:05A02:H10 MA120:H10 BC001619 gi|12804426|gb|BC001619.1BC0016191.1E−299 Homo sapiens, Similar to aldehyde dehydrogenase 5, clone MGC:2230 IMAGE: 3356389, mRNA, complete c 3476 I:3495906:07A02:C10 MA128:C10U19251 gi|2642132|gb|U19251.1HSU19251 Homo 0 sapiens neuronal apoptosisinhibitory protein mRNA, complete cds 3477 I:3704132:03A02:D10 MA112:D10Z49194 gi|974830|emb|Z49194.1HSOBF1 1.3E−102 H. sapiens mRNA foroct-binding factor 3478 I:1636553:03B02:F10 MA114:F10 AB001895gi|2588990|dbj|AB001895.1AB001895 2.8E−130 Homo sapiens mRNA for B120,complete cds 3479 I:1402228:03B02:H10 MA114:H10 BC008588gi|14250316|gb|BC008588.1BC008588 7.8E−170 Homo sapiens, Similar toplastin 3 (T isoform), clone IMAGE: 3447893, mRNA, partial cds 3480I:1361963:01A02:B04 MA104:B04 L13616 gi|439874|gb|L13616.1HUMFAKX2.4E−291 Human focal adhesion kinase (FAK) mRNA, complete cds 3481I:1510424:01A02:D04 MA104:D04 X04481 gi|34627|emb|X04481.1HSMH3C2R  1E−300 Human mRNA for complement component C2 3482 I:2918558:01B02:D04MA106:D04 AF000994 gi|2580573|gb|AF000994.1HSAF000994 8.8E−285 Homosapiens ubiquitous TPR motif, Y isoform (UTY) mRNA, alternativetranscript 3, complete cds 3483 I:1731061:01A02:D10 MA104:D10 BC000418gi|12653298|gb|BC000418.1BC000418   1E−300 Homo sapiens,ectodermal-neural cortex (with BTB-like domain), clone MGC: 8659 IMAGE:2964376, mRNA 3484 I:2579602:04A02:A04 MA116:A04 BC005128gi|13477308|gb|BC005128.1BC005128   1E−300 Homo sapiens, ribosomalprotein L7a, clone MGC: 10607 IMAGE: 3938260, mRNA, complete cds 3485I:2824181:04B02:A04 MA118:A04 BC004900 gi|13436172|gb|BC004900.1BC004900  1E−300 Homo sapiens, ribosomal protein L13a, clone IMAGE: 3545758,mRNA, partial cds 3486 I:2123183:04A02:B04 MA116:B04 BC001164gi|12654652|gb|BC001164.1BC001164 2.1E−198 Homo sapiens, proteasome(prosome, macropain) 26S subunit, non-ATPase, 8, clone MGC: 1660 IMAGE:35 3487 I:1958560:04A02:C10 MA116:C10 0.0522 BC016147gi|16359382|gb|BC016147.1BC016147 1.5E−277 Homo sapiens, clone MGC: 9485IMAGE: 3921259, mRNA, complete cds 3488 I:1447903:04A02:G10 MA116:G10AK056274 gi|16551627|dbj|AK056274.1AK056274 2.2E−48 Homo sapiens cDNAFLJ31712 fis, clone NT2RI2006445, moderately similar to INSULIN-LIKEGROWTH FA 3489 I:1875576:02A02:E10 MA108:E10 U04897gi|451563|gb|U04897.1HSU04897 Human 1.1E−140 orphan hormone nuclearreceptor RORalpha1 mRNA, complete cds 3490 I:1709457:02B02:G10 MA110:G10X65873 gi|34082|emb|X65873.1HSKHCMR 0 H. sapiens mRNA for kinesin (heavychain) 3491 I:2155675:08B01:G05 MA133:G05 0.83871 3492I:1635069:07A01:A05 MA127:A05 D15049 gi|475003|dbj|D15049.1HUMSAP1C3.5E−197 Homo sapiens mRNA for protein tyrosine phosphatase precursor,complete cds 3493 I:1453445:07A01:G05 MA127:G05 0.07788 BC001784gi|13937607|gb|BC001784.1BC001784 1.2E−265 Homo sapiens, Similar toacidic 82 kDa protein mRNA, clone IMAGE: 3542384, mRNA 3494I:3002566:07A01:D11 MA127:D11 D26350 gi|450468|dbj|D26350.1HUMHT2I Human0 mRNA for type 2 inositol 1,4,5- trisphosphate receptor, complete cds3495 I:1631511:06A01:C05 MA123:C05 BC001454gi|12655192|gb|BC001454.1BC001454 0 Homo sapiens, phosphoenolpyruvatecarboxykinase 2 (mitochondrial), clone MGC: 1492 IMAGE: 3138368, 3496I:1610523:06A01:H05 MA123:H05 L19183 gi|307154|gb|L19183.1HUMMAC30X 0Human MAC30 mRNA, 3′ end 3497 I:3297656:06B01:E11 MA125:E11 D14530gi|414348|dbj|D14530.1HUMRSPT   5E−277 Human homolog of yeast ribosomalprotein S28, complete cds 3498 I:2509730:06B01:H11 MA125:H11 X91788gi|1001874|emb|X91788.1HSICLNGEN 0 H. sapiens mRNA for Icln protein 3499I:2121863:03B01:D05 MA113:D05 BC002738 gi|12803796|gb|BC002738.1BC0027386.9E−47 Homo sapiens, cysteine-rich protein 1 (intestinal), clone MGC:3888 IMAGE: 3631097, mRNA, complete 3500 I:1413704:03B01:E05 MA113:E05NM_003903 gi|14110370|ref|NM_003903.2 Homo 8.5E−254 sapiens CDC16 celldivision cycle 16 homolog (S. cerevisiae) (CDC16), mRNA 3501I:1626232:03A01:A11 MA111:A11 AF048700 gi|2935439|gb|AF048700.1AF0487003.5E−203 Homo sapiens gastrointestinal peptide (PEC-60) mRNA, completecds 3502 I:2354446:01B01:B05 MA105:B05 AF131913gi|4928275|gb|AF131913.1AF131913 1.2E−218 Homo sapiens alpha-(1,3/1,4)-fucosyltransferase (FT3B) mRNA, complete cds 3503 I:2916753:01B01:E05MA105:E05 X62534 gi|32332|emb|X62534.1HSHMG2 3.9E−179 H. sapiens HMG-2mRNA 3504 I:2555034:01A01:A11 MA103:A11 0.09272 U39196gi|1055027|gb|U39196.1HSU39196 9.4E−151 Human clone hGIRK1 G-proteincoupled inwardly rectifying potassium channel mRNA, complete cds 3505I:2804190:01B01:D11 MA105:D11 BC004300 gi|13279166|gb|BC004300.1BC0043002.8E−166 Homo sapiens, Similar to villin-like, clone MGC: 10896 IMAGE:3622951, mRNA, complete cds 3506 I:1814488:01A01:E11 MA103:E11 AF044773gi|3002950|gb|AF044773.1AF044773 8.8E−208 Homo sapiens breakpointcluster region protein 1 (BCRG1) mRNA, complete cds 3507I:2474163:01B01:E11 MA105:E11 J03037 gi|179771|gb|J03037.1HUMCAIIA Human1.2E−143 carbonic anhydrase II mRNA, complete cds 3508I:1402967:01A01:G11 MA103:G11 Y00651 gi|34504|emb|Y00651.1HSMCP Human1.5E−227 mRNA for membrane cofactor protein 3509 I:2821541:10A01:D11MA64:D11 0.356 3510 I:2888814:04B01:A05 MA117:A05 Y10806gi|1808645|emb|Y10806.1HSY10806   1E−300 H. sapiens mRNA for argininemethyltransferase, splice variant, 1316 bp 3511 I:1451005:04A01:C05MA115:C05 BC001771 gi|12804688|gb|BC001771.1BC001771 3.3E−200 Homosapiens, general transcription factor IIF, polypeptide 2 (30 kDsubunit), clone MGC: 1502 IMAG 3512 I:1457726:04A01:H05 MA115:H05AK001686 gi|7023098|dbj|AK001686.1AK001686 3.9E−209 Homo sapiens cDNAFLJ10824 fis, clone NT2RP4001086 3513 I:2883195:04B01:H05 MA117:H05BC000672 gi|12653772|gb|BC000672.1BC000672   1E−290 Homo sapiens,guanine nucleotide binding protein (G protein), beta polypeptide 2-like1, clone MG 3514 I:1603605:04A01:G11 MA115:G11 0.04363 D38305gi|1580723|dbj|D38305.1HUMTOB 1.3E−268 Human mRNA for Tob, complete cds3515 I:2832224:04A01:H11 MA115:H11 L09604 gi|177899|gb|L09604.1HUMA4Homo 0 sapiens differentiation-dependent A4 protein mRNA, complete cds3516 I:2231364:02A01:A05 MA107:A05 D87469 gi|1665820|dbj|D87469.1D87469Human 0 mRNA for KIAA0279 gene, partial cds 3517 I:1595081:02B01:F11MA109:F11 S36219 gi|249623|gb|S36219.1S36219   1E−300 prostaglandin G/Hsynthase {alternative splicing product} [human, lung fibroblast, cloneHCO-T9, mRNA, 3518 I:1877913:05B02:C05 MA122:C05 U51903gi|1262925|gb|U51903.1HSU51903   1E−300 Human RasGAP-related protein(IQGAP2) mRNA, complete cds 3519 I:1666130:05B02:F05 MA122:F05 X05790gi|28535|emb|X05790.1HSAGALAR 0 Human mRNA for alpha-galactosidase A (EC3.2.1-22) 3520 I:1709995:05B02:H05 MA122:H05 U78525gi|2558667|gb|U78525.1HSU78525 Homo 8.3E−279 sapiens eukaryotictranslation initiation factor (eIF3) mRNA, complete cds 3521I:3872557:07A02:B05 MA128:B05 NM_000518 gi|13788565|ref|NM_000518.3 Homo0 sapiens hemoglobin, beta (HBB), mRNA 3522 I:2734906:07A02:E11MA128:E11 NM_001997 gi|17981709|ref|NM_001997.2 Homo 1.3E−277 sapiensFinkel-Biskis-Reilly murine sarcoma virus (FBR-MuSV) ubiquitouslyexpressed (fox derived); 3523 I:1798585:06A02:B05 MA124:B05 BC008767gi|14250615|gb|BC008767.1BC008767 0 Homo sapiens, Similar toacyl-Coenzyme A oxidase 1, palmitoyl, clone MGC: 1198 IMAGE: 3051501,mRNA 3524 I:1683389:06A02:F05 MA124:F05 BC015335gi|15929831|gb|BC015335.1BC015335 0 Homo sapiens, immature coloncarcinoma transcript 1, clone MGC: 21251 IMAGE: 4418983, mRNA, complet3525 I:1704517:06A02:G05 MA124:G05 BC005820gi|14710649|gb|BC005820.1BC005820 0 Homo sapiens, clone IMAGE: 3937549,mRNA 3526 I:2792982:06B02:H05 MA126:H05 X71345gi|405755|emb|X71345.1HSTRYIVB 0 H. sapiens mRNA for trypsinogen IV b-form 3527 I:3511355:06B02:D11 MA126:D11 NM_001002gi|16933547|ref|NM_001002.2 Homo   1E−300 sapiens ribosomal protein,large, P0 (RPLP0), transcript variant 1, mRNA 3528 I:1738060:03A02:A05MA112:A05 BC000508 gi|12653472|gb|BC000508.1BC000508 1.1E−243 Homosapiens, proteasome (prosome, macropain) subunit, beta type, 1, cloneMGC: 8505 IMAGE: 2822268 3529 I:1810821:03B02:B05 MA114:B05 BC016956gi|16877417|gb|BC016956.1BC016956   7E−217 Homo sapiens, clone MGC:21520 IMAGE: 3900854, mRNA, complete cds 3530 I:2451279:03A02:E05MA112:E05 BC009868 gi|14602690|gb|BC009868.1BC009868 1.8E−167 Homosapiens, replication protein A3 (14 kD), clone MGC: 16404 IMAGE:3940438, mRNA, complete cds 3531 I:1431166:03B02:E05 MA114:E05 BC010444gi|14714612|gb|BC010444.1BC010444 5.5E−230 Homo sapiens, matrilin 2,clone MGC: 17281 IMAGE: 4215380, mRNA, complete cds 3532I:2949427:03B02:A11 MA114:A11 BC006794 gi|13905021|gb|BC006794.1BC0067943.2E−225 Homo sapiens, Similar to interferon induced transmembraneprotein 3 (1-8U), clone MGC: 5225 IMAGE: 3533 I:1458366:03B02:E11MA114:E11 AF009202 gi|2454507|gb|AF009202.1AF009202 3.7E−290 Homosapiens YAC clone 136A2 unknown mRNA, 3′untranslated region 3534I:1525881:03B02:G11 MA114:G11 AF368463 gi|14583005|gb|AF368463.1AF3684638.5E−176 Homo sapiens carboxypeptidase M mRNA, complete cds 3535I:2071473:01A02:E05 MA104:E05 X17567 gi|36512|emb|X17567.1HSSNRNPB 0 H.sapiens RNA for snRNP protein B 3536 I:2481012:01A02:C11 MA104:C11BC001625 gi|12804436|gb|BC001625.1BC001625 1.6E−236 Homo sapiens,Similar to for protein disulfide isomerase-related, clone MGC: 1259IMAGE: 3537659, m 3537 I:2816931:01B02:C11 MA106:C11 D88827gi|2342505|dbj|D88827.1D88827 Homo 4.2E−159 sapiens mRNA for zinc fingerprotein FPM315, complete cds 3538 I:1806769:01B02:F11 MA106:F11NM_005971 gi|11612675|ref|NM_005971.2 Homo 8.8E−242 sapiens FXYDdomain-containing ion transport regulator 3 (FXYD3), transcript variant1, mRNA 3539 I:2636634:04B02:A11 MA118:A11 L32137gi|602449|gb|L32137.1HUMCOMP 2.5E−210 Human germline oligomeric matrixprotein (COMP) mRNA, complete cds 3540 I:1649959:02B02:E11 MA110:E11BC002700 gi|12803726|gb|BC002700.1BC002700 2.5E−254 Homo sapiens,Similar to keratin 7, clone MGC: 3625 IMAGE: 3610347, mRNA, complete cds3541 I:1633719:02B02:F11 MA110:F11 J05428 gi|340079|gb|J05428.1HUMUDPGTA3.8E−290 Human 3,4-catechol estrogen UDP- glucuronosyltransferase mRNA,complete cds 3542 I:1901035:02B02:G11 MA110:G11 AF081513gi|5725637|gb|AF081513.1AF081513 1.2E−143 Homo sapiens TGF-beta typesecreted signaling protein LEFTYA mRNA, complete cds 3543I:2503879:08B01:C12 MA133:C12 AF150733 gi|7688664|gb|AF150733.1AF1507333.9E−237 Homo sapiens AD-014 protein mRNA, complete cds 3544I:2383065:07B01:B06 MA129:B06 AJ335311gi|15879729|emb|AJ335311.1HSA335311 3.7E−50 Homo sapiens genomicsequence surrounding NotI site, clone NR1-WB8C 3545 I:3357245:07A01:F06MA127:F06 X95073 gi|2879814|emb|X95073.1HSTRAXGEN 0 H. sapiens mRNA fortranslin associated protein X 3546 I:2832314:07A01:G06 MA127:G06 M26252gi|338826|gb|M26252.1HUMTCBA 7.8E−279 Human TCB gene encoding cytosolicthyroid hormone-binding protein, complete cds 3547 I:3667096:07A01:D12MA127:D12 BC003412 gi|13097323|gb|BC003412.1BC003412   1E−300 Homosapiens, cyclophilin, clone MGC: 5016 IMAGE: 3451034, mRNA, complete cds3548 I:1798283:06A01:D06 MA123:D06 BC016835gi|16877126|gb|BC016835.1BC016835   1E−300 Homo sapiens, Similar tosynaptophysin- like protein, clone MGC: 10011 IMAGE: 3883697, mRNA,complet 3549 I:1648206:03A01:B06 MA111:B06 AJ420535gi|17066399|emb|AJ420535.1HSA420535 6.2E−264 Homo sapiens mRNA fulllength insert cDNA clone EUROIMAGE 993611 3550 I:3360476:03B01:B12MA113:B12 Y08768 gi|1877211|emb|Y08768.1HSIL13 1.4E−177 H. sapiens mRNAfor IL-13 receptor 3551 I:2500511:03B01:C12 MA113:C12 AJ001531gi|2661423|emb|AJ001531.1HSNEUROTR 3.9E−265 Homo sapiens mRNA forneurotrypsin 3552 I:1730806:03B01:D12 MA113:D12 AL049705gi|4678821|emb|AL049705.1HS262D122 7.8E−220 Human gene from PAC 262D12,chromosome 1 3553 I:2479074:01B01:C06 MA105:C06 AF096304gi|4191395|gb|AF096304.1AF096304 0 Homo sapiens putative sterolreductase SR-1 (TM7SF2) mRNA, complete cds 3554 I:1635004:01B01:E06MA105:E06 BC003661 gi|13177786|gb|BC003661.1BC003661 4.6E−231 Homosapiens, lectin, galactoside-binding, soluble, 4 (galectin 4), cloneMGC: 698 IMAGE: 2967411, 3555 I:2378569:01B01:G06 MA105:G06 BC000341gi|12653146|gb|BC000341.1BC000341 8.7E−236 Homo sapiens, signal sequencereceptor, beta (translocon-associated protein beta), clone MGC: 85663556 I:2207849:01A01:D12 MA103:D12 X65019 gi|33792|emb|X65019.1HSIL1BRNA0 H. sapiens mRNA for interleukin-1B converting enzyme 3557I:1504554:01A01:F12 MA103:F12 0.1646 U43843gi|1532120|gb|U43843.1HSU43843 4.6E−151 Human h-neuro-d4 protein mRNA,complete cds 3558 I:2989991:04B01:A06 MA117:A06 AF400442gi|15217078|gb|AF400442.1AF400442   1E−300 Homo sapiens pigmentepithelium-derived factor (SERPINF1) mRNA, complete cds 3559I:2852561:04B01:B06 MA117:B06 J02769 gi|177206|gb|J02769.1HUM4F2A Human1.4E−255 4F2 antigen heavy chain mRNA, complete cds 3560I:2832839:04A01:C12 MA115:C12 NM_006399 gi|5453562|ref|NM_006399.1 Homo2.6E−138 sapiens basic leucine zipper transcription factor, ATF-like(BATF), mRNA 3561 I:2845548:04B01:E12 MA117:E12 AY034482gi|15809587|gb|AY034482.1 Homo 3.1E−278 sapiens hnRNP Q2 mRNA, completecds 3562 I:1251819:02B01:B06 MA109:B06 X78669gi|469884|emb|X78669.1HSERC55R 9.1E−288 H. sapiens ERC-55 mRNA 3563I:1672930:02B01:D06 MA109:D06 X83617 gi|620082|emb|X83617.1HSRANBP14.7E−274 H. sapiens mRNA for RanBP1 3564 I:2122820:02B01:E06 MA109:E06BC001738 gi|12804628|gb|BC001738.1BC001738 3.9E−234 Homo sapiens,Similar to ubiquitin- conjugating enzyme E2G 2 (homologous to yeastUBC7), clone MGC 3565 I:2174920:02A01:H06 MA107:H06 BC006230gi|13623260|gb|BC006230.1BC006230 9.5E−260 Homo sapiens,lysophospholipase-like, clone MGC: 10338 IMAGE: 3945191, mRNA, completecds 3566 I:1875994:05B02:E06 MA122:E06 BC002638gi|12803606|gb|BC002638.1BC002638 2.2E−217 Homo sapiens, hypotheticalprotein, clone MGC: 3365 IMAGE: 3608062, mRNA, complete cds 3567I:1858644:05A02:G06 MA120:G06 M55268 gi|177837|gb|M55268.1HUMA1CKII3.4E−284 Human casein kinase II alpha' subunit mRNA, complete cds 3568I:1700047:06A02:E06 MA124:E06 BC000405 gi|12653272|gb|BC000405.1BC0004051.4E−224 Homo sapiens, small nuclear ribonucleoprotein polypeptide A,clone MGC: 8567 IMAGE: 2822987, mRNA, 3569 I:1718257:06B02:E06 MA126:E06AF020760 gi|5870864|gb|AF020760.2AF020760 0 Homo sapiens serine protease(OMI) mRNA, complete cds 3570 I:1612306:06A02:F06 MA124:F06 BC002594gi|12803530|gb|BC002594.1BC002594 4.5E−271 Homo sapiens, dolichyl-diphosphooligosaccharide-protein glycosyltransferase, clone MGC: 2191IMAGE 3571 I:1637427:06A02:F12 MA124:F12 U31659gi|1136305|gb|U31659.1HSU31659 7.5E−217 Human TBP-associated factorTAFII80 mRNA, complete cds 3572 I:2513883:03A02:B12 MA112:B12 X76717gi|435674|emb|X76717.1HSMT1L 2.1E−142 H. sapiens MT-11 mRNA 3573I:2645840:01A02:G06 MA104:G06 X97795 gi|1495482|emb|X97795.1HSRAD541.7E−295 H. sapiens mRNA homologous to S. cerevisiae RAD54 3574I:1737403:01A02:A12 MA104:A12 Z29067 gi|479172|emb|Z29067.1HSNEK3R 0 H.sapiens nek3 mRNA for protein kinase 3575 I:1733522:01B02:H12 MA106:H12BC017880 gi|17389723|gb|BC017880.1BC017880 7.7E−95 Homo sapiens, cloneMGC: 22754 IMAGE: 4277855, mRNA, complete cds 3576 RG:160664:10006:E07MA155:E07 NM_020975 gi|10862702|ref|NM_020975.1 Homo 1.7E−298 sapiensret proto-oncogene (multiple endocrine neoplasia and medullary thyroidcarcinoma 1, Hirsch 3577 I:747335:16A01:E01 MA87:E01 NM_000985gi|14591906|ref|NM_000985.2 Homo 3.1E−272 sapiens ribosomal protein L17(RPL17), mRNA 3578 I:2085191:16A01:H01 MA87:H01 M22612gi|521215|gb|M22612.1HUMTRPSGNA   1E−287 Human pancreatic trypsin 1(TRY1) mRNA, complete cds 3579 I:1211126:16A01:E07 MA87:E07 Y13901gi|2832349|emb|Y13901.1HSFGFR4G   1E−300 Homo sapiens FGFR-4 gene 3580RG:669310:10010:C01 MA159:C01 BC000833 gi|12654054|gb|BC000833.1BC0008330 Homo sapiens, clone IMAGE: 3455871, mRNA, partial cds 3581RG:730402:10010:H01 MA159:H01 0.225 BC000633gi|12653696|gb|BC000633.1BC000633 2.1E−38 Homo sapiens, TTK proteinkinase, clone MGC: 865 IMAGE: 3343925, mRNA, complete cds 3582RG:1047541:10012:C07 MA161:C07 AF156965 gi|5731112|gb|AF156965.1AF1569650 Homo sapiens translocon-associated protein alpha subunit mRNA,complete cds 3583 RG:1161753:10012:E07 MA161:E07 X12883gi|30310|emb|X12883.1HSCYKT18 0 Human mRNA for cytokeratin 18 3584I:1218464:17B01:E01 MA93:E01 0.47248 3585 I:958633:17B01:G07 MA93:G07AF267862 gi|12006050|gb|AF267862.1AF267862 1.8E−180 Homo sapiens DC44mRNA, complete cds 3586 I:1602726:09B01:B07 MA137:B07 0.45675 3587RG:205212:10007:B01 MA156:B01 AF069747 gi|4106379|gb|AF069747.1AF0697476.1E−227 Homo sapiens MTG8-like protein MTGR1a mRNA, complete cds 3588RG:207395:10007:B07 MA156:B07 Z74616 gi|1418929|emb|Z74616.1HSPPA2ICO 0H. sapiens mRNA for prepro-alpha2(I) collagen 3589 I:349535:16B02:G01MA90:G01 0.19957 3590 I:2323525:16A02:H01 MA88:H01 0.30114 3591I:1965049:16B02:D07 MA90:D07 AF113007 gi|6642737|gb|AF113007.1AF1130074.1E−162 Homo sapiens PRO0066 mRNA, complete cds 3592I:2054436:16A02:G07 MA88:G07 0.15978 3593 RG:1506197:10013:F01 MA162:F01NM_052841 gi|17017992|ref|NM_052841.2 Homo   2E−137 sapiensserine/threonine kinase 22C (spermiogenesis associated) (STK22C), mRNA3594 RG:1871436:10015:G01 MA164:G01 X60489 gi|31099|emb|X60489.1HSEF1BHuman 0 mRNA for elongation factor-1-beta 3595 RG:1705470:10015:B07MA164:B07 L38734 gi|769675|gb|L38734.1HUMHTK Homo 2.1E−282 sapienshepatoma transmembrane kinase ligand (HTK ligand) mRNA, complete cds3596 I:546910:17B02:B07 MA94:B07 AK002212gi|7023953|dbj|AK002212.1AK002212 3.3E−97 Homo sapiens cDNA FLJ11350fis, clone Y79AA1001647 3597 I:1799023:09B02:F01 MA138:F01 AK023003gi|10434717|dbj|AK023003.1AK023003 2.5E−164 Homo sapiens cDNA FLJ12941fis, clone NT2RP2005116, moderately similar to PUTATIVE EUKARYOTIC TR3598 I:2380380:09B02:H01 MA138:H01 AF268037gi|8745546|gb|AF268037.1AF268037 0 Homo sapiens C8ORF4 protein (C8ORF4)mRNA, complete cds 3599 I:2319269:18A01:F02 MA95:F02 AK022882gi|10434533|dbj|AK022882.1AK022882 1.1E−206 Homo sapiens cDNA FLJ12820fis, clone NT2RP2002736 3600 I:2296344:18A01:D08 MA95:D08 AJ387747gi|6562532|emb|AJ387747.1HSA387747 3.6E−225 Homo sapiens mRNA for sialin3601 RG:155066:10006:E02 MA155:E02 BC018851gi|17402989|gb|BC018851.1BC018851 2.2E−279 Homo sapiens, clone IMAGE:3141444, mRNA 3602 RG:180135:10006:G02 MA155:G02 L37043gi|852056|gb|L37043.1HUMCSNK1E 0 Homo sapiens casein kinase I epsilonmRNA, complete cds 3603 RG:178093:10006:F08 MA155:F08 AL117430gi|5911865|emb|AL117430.1HSM800939 0 Homo sapiens mRNA; cDNADKFZp434D156 (from clone DKFZp434D156); partial cds 3604RG:184042:10006:G08 MA155:G08 BC017459 gi|16907188|gb|BC017459.1BC0174595.3E−240 Homo sapiens, clone IMAGE: 4645230, mRNA 3605I:1741643:16A01:A02 MA87:A02 D38551 gi|1531549|dbj|D38551.1HUMORF0051.1E−209 Human mRNA for KIAA0078 gene, complete cds 3606RG:928026:10012:B02 MA161:B02 AL050147gi|4884153|emb|AL050147.1HSM800223 1.3E−218 Homo sapiens mRNA; cDNADKFZp586E0820 (from clone DKFZp586E0820); partial cds 3607RG:1032969:10012:C02 MA161:C02 AF261717 gi|8926204|gb|AF261717.1AF2617170 Homo sapiens SAR1 (SAR1) mRNA, complete cds 3608 RG:1322660:10012:H02MA161:H02 L05144 gi|189944|gb|L05144.1HUMPHOCAR 5.3E−283 Homo sapiens(clone lamda-hPEC-3) phosphoenolpyruvate carboxykinase (PCK1) mRNA,complete cds 3609 RG:968474:10012:B08 MA161:B08 Y11339gi|7576275|emb|Y11339.2HSY11339 1.7E−227 Homo sapiens mRNA for GalNAcalpha-2, 6-sialyltransferase I, long form 3610 RG:1047592:10012:C08MA161:C08 X05803 gi|34080|emb|X05803.1HSKERUV   1E−300 Human radiatedkeratinocyte mRNA 266 (keratin-related protein) 3611 I:617750:17B01:E08MA93:E08 0.19395 3612 I:2808775:09B01:G02 MA137:G02 0.40171 3613I:966692:18A02:B08 MA96:B08 0.32029 AK055949gi|16550804|dbj|AK055949.1AK055949 3.7E−123 Homo sapiens cDNA FLJ31387fis, clone NT2NE1000018, weakly similar to SUPPRESSOR PROTEIN SRP40 3614RG:209240:10007:C02 MA156:C02 BC001737 gi|12804626|gb|BC001737.1BC001737  3E−192 Homo sapiens, clone IMAGE: 3354010, mRNA, partial cds 3615RG:223355:10007:D02 MA156:D02 Z11696 gi|23882|emb|Z11696.1HS44KDAP5.4E−252 H. sapiens 44 kDa protein kinase related to rat ERK1 3616RG:267629:10007:H02 MA156:H02 U73824 gi|1857236|gb|U73824.1HSU738243.2E−269 Human p97 mRNA, complete cds 3617 I:2246234:16B02:C08 MA90:C083618 RG:1696513:10015:B02 MA164:B02 0.07275 AF377330gi|14278713|gb|AF377330.2AF377330 0 Homo sapiens urokinase-typeplasminogen activator (PLAU) gene, complete cds 3619RG:1733895:10015:D02 MA164:D02 BC009470gi|14495716|gb|BC009470.1BC009470 0 Homo sapiens, protein kinase,interferon- inducible double stranded RNA dependent activator, clone3620 RG:1353930:10013:A08 MA162:A08 U86453gi|2317893|gb|U86453.1HSU86453 6.4E−295 Human phosphatidylinositol3-kinase catalytic subunit p110delta mRNA, complete cds 3621RG:1881947:10015:G08 MA164:G08 BC005858gi|13543399|gb|BC005858.1BC005858 0 Homo sapiens, clone MGC: 3255 IMAGE:3506187, mRNA, complete cds 3622 RG:166575:10006:F03 MA155:F03 AK057849gi|16553810|dbj|AK057849.1AK057849   1E−300 Homo sapiens cDNA FLJ25120fis, clone CBR06020 3623 I:1998994:16A01:A03 MA87:A03 J04205gi|178686|gb|J04205.1HUMANTLAA 1.6E−258 Human La protein mRNA, completecds 3624 I:1953051:16A01:D03 MA87:D03 BC004138gi|13278716|gb|BC004138.1BC004138   2E−276 Homo sapiens, ribosomalprotein L6, clone MGC: 1635 IMAGE: 2823733, mRNA, complete cds 3625I:518826:16A01:E03 MA87:E03 BC007771 gi|14043585|gb|BC007771.1BC0077712.8E−266 Homo sapiens, dual specificity phosphatase 2, clone MGC: 12703IMAGE: 4297852, mRNA, complete cds 3626 I:81490:16A01:B09 MA87:B09BC007942 gi|14044027|gb|BC007942.1BC007942 1.9E−270 Homo sapiens,nucleolar autoantigen (55 kD) similar to rat synaptonemal complexprotein, clone MGC 3627 RG:1256163:10012:F03 MA161:F03 M36501gi|177871|gb|M36501.1HUMA2MGL   1E−300 Human alpha-2-macroglobulin mRNA,3′ end 3628 RG:1132085:10012:D09 MA161:D09 BC006510gi|13676353|gb|BC006510.1BC006510 0 Homo sapiens, Similar to cyclin B1,related sequence 1, clone MGC: 2548 IMAGE: 2963100, mRNA, compl 3629I:2132717:17B01:C09 MA93:C09 AB058749 gi|14017908|dbj|AB058749.1AB0587493.8E−256 Homo sapiens mRNA for KIAA1846 protein, partial cds 3630I:1998428:17B01:F09 MA93:F09 AF115926 gi|17998664|gb|AF115926.1AF1159266.9E−208 Homo sapiens XAG-2 homolog long protein (HPC8) mRNA, completecds 3631 RG:206694:10007:B03 MA156:B03 X00588gi|31113|emb|X00588.1HSEGFPRE   1E−300 Human mRNA for precursor ofepidermal growth factor receptor 3632 RG:261714:10007:F09 MA156:F09AF116618 gi|7959738|gb|AF116618.1AF116618 0 Homo sapiens PRO1038 mRNA,complete cds 3633 I:1461515:16A02:C03 MA88:C03 0.3525 3634I:338859:16A02:H03 MA88:H03 0.27273 3635 I:1425861:16A02:G09 MA88:G090.4929 3636 I:1928644:16B02:H09 MA90:H09 0.34967 AK055711gi|16550506|dbj|AK055711.1AK055711 7.1E−131 Homo sapiens cDNA FLJ31149fis, clone IMR322001491, moderately similar to Rattus norvegicus tric3637 RG:1404414:10013:C03 MA162:C03 U01038 gi|393016|gb|U01038.1HSU01038Human 6.5E−277 pLK mRNA, complete cds 3638 RG:1415437:10013:D03MA162:D03 BC001190 gi|12654700|gb|BC001190.1BC001190 0 Homo sapiens,Similar to creatine kinase, brain, clone MGC: 3160 IMAGE: 3354679, mRNA,complete cds 3639 RG:1734353:10015:D03 MA164:D03 BC002555gi|12803460|gb|BC002555.1BC002555 0 Homo sapiens, CDC-like kinase 3,clone MGC: 1777 IMAGE: 3138580, mRNA, complete cds 3640RG:1872251:10015:G03 MA164:G03 Y17151 gi|4826562|emb|Y17151.2HSY171511.7E−31 Homo sapiens mRNA for multidrug resistance protein 3 (ABCC3)3641 RG:1354408:10013:A09 MA162:A09 AF257466gi|8453155|gb|AF257466.1AF257466 3.7E−290 Homo sapiensN-acetylneuraminic acid phosphate synthase mRNA, complete cds 3642RG:1690198:10015:A09 MA164:A09 X90563 gi|1480099|emb|X90563.1HSPPARGAM 0H. sapiens mRNA for peroxisome proliferactor activated receptor gamma3643 RG:1476452:10013:E09 MA162:E09 BC007276gi|13938296|gb|BC007276.1BC007276   1E−300 Homo sapiens, Similar to heatshock cognate 71-kd protein, clone MGC: 15597 IMAGE: 3162067, mRNA, c3644 I:2069305:09B02:F03 MA138:F03 BC015139gi|15929410|gb|BC015139.1BC015139 0 Homo sapiens, clone IMAGE: 4040789,mRNA, partial cds 3645 I:1966067:18B01:H04 MA97:H04 AF062916gi|3941523|gb|AF062916.1AF062916 3.6E−22 Arabidopsis thaliana putativetranscription factor (MYB92) mRNA, complete cds 3646 I:2128547:18B01:A10MA97:A10 AF151839 gi|4929630|gb|AF151839.1AF151839 4.6E−268 Homo sapiensCGI-81 protein mRNA, complete cds 3647 RG:149960:10006:D04 MA155:D04BC017483 gi|17028354|gb|BC017483.1BC017483 3.9E−237 Homo sapiens, cloneIMAGE: 3506553, mRNA 3648 RG:171569:10006:F04 MA155:F04 M64174gi|190734|gb|M64174.1HUMPTKJAK1   1E−300 Human protein-tyrosine kinase(JAK1) mRNA, complete cds 3649 RG:178638:10006:F10 MA155:F10 BC004408gi|13325179|gb|BC004408.1BC004408 1.1E−225 Homo sapiens, Similar tohigh-mobility group 20B, clone MGC: 11001 IMAGE: 3638942, mRNA, completec 3650 RG:195122:10006:H10 MA155:H10 Z11695gi|23878|emb|Z11695.1HS40KDAP 4.3E−271 H. sapiens 40 kDa protein kinaserelated to rat ERK2 3651 I:814216:16A01:F10 MA87:F10 BC006395gi|13623564|gb|BC006395.1BC006395 9.3E−254 Homo sapiens, cell divisioncycle 25B, clone MGC: 12797 IMAGE: 4135465, mRNA, complete cds 3652RG:491163:10010:A04 MA159:A04 BC008767 gi|14250615|gb|BC008767.1BC0087679.3E−232 Homo sapiens, Similar to acyl-Coenzyme A oxidase 1, palmitoyl,clone MGC: 1198 IMAGE: 3051501, mRNA 3653 RG:827185:10012:A04 MA161:A04AK055642 gi|16550422|dbj|AK055642.1AK055642 2.5E−251 Homo sapiens cDNAFLJ31080 fis, clone HSYRA2001615, highly similar to Sus scrofacalcium/calmodu 3654 RG:1129102:10012:D04 MA161:D04 NM_000975gi|15431289|ref|NM_000975.2 Homo   1E−300 sapiens ribosomal protein L11(RPL11), mRNA 3655 RG:730938:10010:H04 MA159:H04 BC000580gi|12653606|gb|BC000580.1BC000580 2.1E−254 Homo sapiens, clone IMAGE:3162218, mRNA, partial cds 3656 RG:925984:10012:A10 MA161:A10 J03358gi|339714|gb|J03358.1HUMTKFER 1.2E−246 Human tyrosine kinase (FER) mRNA,complete cds 3657 RG:668442:10010:B10 MA159:B10 X74764gi|433337|emb|X74764.1HSRPTK 0 H. sapiens mRNA for receptor proteintyrosine kinase 3658 RG:1028911:10012:B10 MA161:B10 U88666gi|1857943|gb|U88666.1HSU88666 Homo   1E−300 sapiens serine kinase SRPK2mRNA, complete cds 3659 RG:684866:10010:C10 MA159:C10 X51521gi|31282|emb|X51521.1HSEZRIN Human   1E−293 mRNA for ezrin 3660RG:1283076:10012:F10 MA161:F10 BC007888gi|14043894|gb|BC007888.1BC007888 0 Homo sapiens, eukaryotic translationinitiation factor 2, subunit 2 (beta, 38 kD), clone MGC: 1417 3661I:627654:17A01:G04 MA91:G04 AF081192 gi|3420798|gb|AF081192.1AF081192 0Homo sapiens histone H2A.F/Z variant (H2AV) mRNA, complete cds 3662I:1833801:17A01:D10 MA91:D10 BC009836 gi|14602636|gb|BC009836.1BC0098361.9E−270 Homo sapiens, clone MGC: 15133 IMAGE: 4098463, mRNA, completecds 3663 I:961473:17B01:H10 MA93:H10 0.20615 AK024678gi|10437017|dbj|AK024678.1AK024678 2.7E−117 Homo sapiens cDNA: FLJ21025fis, clone CAE06758 3664 I:2556708:09B01:B10 MA137:B10 BC018807gi|17402954|gb|BC018807.1BC018807 1.6E−55 Homo sapiens, clone IMAGE:4861487, mRNA 3665 RG:243565:10007:D10 MA156:D10 AF015254gi|4090840|gb|AF015254.1AF015254 8.4E−186 Homo sapiens serine/threoninekinase (STK-1) mRNA, complete cds 3666 RG:266649:10007:G10 MA156:G10AB034951 gi|11526572|dbj|AB034951.1AB034951   1E−300 Homo sapiens HSC54mRNA for heat shock cognate protein 54, complete cds 3667I:2013513:16B02:B04 MA90:B04 AF155913 gi|6435129|gb|AF155913.1AF155913Mus 3.7E−51 musculus putative E1-E2 ATPase mRNA, complete cds 3668I:2312442:16A02:B10 MA88:B10 0.38737 AK021945gi|10433249|dbj|AK021945.1AK021945 1.9E−131 Homo sapiens cDNA FLJ11883fis, clone HEMBA1007178 3669 I:2060626:16A02:D10 MA88:D10 AK055800gi|16550622|dbj|AK055800.1AK055800 1.1E−191 Homo sapiens cDNA FLJ31238fis, clone KIDNE2004864 3670 RG:1415858:10013:D04 MA162:D04 D85759gi|1526445|dbj|D85759.1D85759 Homo 4.8E−271 sapiens mRNA for MNB proteinkinase, complete cds 3671 RG:1517435:10013:F04 MA162:F04 X13546gi|32328|emb|X13546.1HSHMG17G 6.7E−292 Human HMG-17 gene for non-histonechromosomal protein HMG-17 3672 RG:1914716:10015:H04 MA164:H04 X13697gi|36414|emb|X13697.1HSSBLA Human   1E−300 mRNA for ribonucleoproteinSS-B/La 3673 RG:1354528:10013:A10 MA162:A10 AF197898gi|6166494|gb|AF197898.1AF197898 6.7E−298 Homo sapiens nemo-like kinasemRNA, complete cds 3674 RG:1706414:10015:B10 MA164:B10 M36501gi|177871|gb|M36501.1HUMA2MGL 0 Human alpha-2-macroglobulin mRNA, 3′ end3675 I:1998510:17A02:C04 MA92:C04 BC004872gi|13436100|gb|BC004872.1BC004872 1.4E−252 Homo sapiens, clone MGC:11034 IMAGE: 3677618, mRNA, complete cds 3676 I:899118:17B02:G10MA94:G10 AK055564 gi|16550323|dbj|AK055564.1AK055564   4E−159 Homosapiens cDNA FLJ31002 fis, clone HLUNG2000004 3677 I:2680168:09B02:B04MA138:B04 AL050071 gi|4884302|emb|AL050071.1HSM800396 0 Homo sapiensmRNA; cDNA DKFZp566B0846 (from clone DKFZp566B0846); partial cds 3678I:1354558:09B02:E04 MA138:E04 AK054675gi|16549267|dbj|AK054675.1AK054675   1E−156 Homo sapiens cDNA FLJ30113fis, clone BNGH42000474 3679 I:1665871:09B02:F10 MA138:F10 AF288394gi|12620197|gb|AF288394.1AF288394 0 Homo sapiens C1orf19 mRNA, partialcds 3680 I:1922084:18B01:C05 MA97:C05 AK000057gi|7019894|dbj|AK000057.1AK000057 1.3E−246 Homo sapiens cDNA FLJ20050fis, clone COL00688 3681 I:2307946:18A01:B11 MA95:B11 BC016150gi|16740553|gb|BC016150.1BC016150 8.9E−226 Homo sapiens, Similar toCAP-binding protein complex interacting protein 2, clone IMAGE: 3637027,3682 I:1923572:18B01:C11 MA97:C11 AL049959gi|4884211|emb|AL049959.1HSM800304 2.3E−154 Homo sapiens mRNA; cDNADKFZp564K1023 (from clone DKFZp564K1023) 3683 RG:171993:10006:F05MA155:F05 0.31835 AK057735 gi|16553657|dbj|AK057735.1AK057735 3.9E−142Homo sapiens cDNA FLJ25006 fis, clone CBL00989 3684 RG:129317:10006:B11MA155:B11 AF103796 gi|4185795|gb|AF103796.1AF103796   1E−300 Homosapiens placenta-specific ATP- binding cassette transporter (ABCP) mRNA,complete cds 3685 RG:153244:10006:D11 MA155:D11 L06139gi|292823|gb|L06139.1HUMTEKRPTK 1.1E−299 Homo sapiens receptorprotein-tyrosine kinase (TEK) mRNA, complete cds 3686RG:196236:10006:H11 MA155:H11 AF359246 gi|13991617|gb|AF359246.1AF359246  5E−249 Homo sapiens fibroblast growth factor receptor 4 variant mRNA,complete cds 3687 I:557538:16A01:C11 MA87:C11 BC013142gi|15341912|gb|BC013142.1BC013142 1.1E−240 Homo sapiens, interleukin 1,alpha, clone MGC: 9225 IMAGE: 3875617, mRNA, complete cds 3688I:782235:16A01:F11 MA87:F11 K01228 gi|180391|gb|K01228.1HUMCG1PA1  9E−251 Human proalpha 1 (I) chain of type I procollagen mRNA (partial)3689 RG:1257341:10012:F05 MA161:F05 BC007952gi|14044057|gb|BC007952.1BC007952   1E−300 Homo sapiens, pyruvatekinase, muscle, clone MGC: 14360 IMAGE: 4299213, mRNA, complete cds 3690RG:727387:10010:G05 MA159:G05 BC001413 gi|13937593|gb|BC001413.1BC0014130 Homo sapiens, clone IMAGE: 3140866, mRNA 3691 RG:1145235:10012:D11MA161:D11 BC007540 gi|14043108|gb|BC007540.1BC007540 3.4E−71 Homosapiens, clone IMAGE: 3609337, mRNA, partial cds 3692RG:725145:10010:F11 MA159:F11 AJ000512 gi|2463200|emb|AJ000512.1HSSGK8.4E−264 Homo sapiens sgk gene 3693 RG:740079:10010:H11 MA159:H11 M14505gi|456426|gb|M14505.1HUMCDPK 0 Human (clone PSK-J3) cyclin-dependentprotein kinase mRNA, complete cds., 3694 I:1873176:09B01:E05 MA137:E05BC001909 gi|12804912|gb|BC001909.1BC001909 0 Homo sapiens, clone IMAGE:3537447, mRNA, partial cds 3695 I:2081974:09B01:D11 MA137:D11 AK057078gi|16552660|dbj|AK057078.1AK057078 0 Homo sapiens cDNA FLJ32516 fis,clone SMINT1000103, highly similar to Homo sapiens ankyrin repea 3696I:2107723:18A02:G05 MA96:G05 AK000193 gi|7020116|dbj|AK000193.1AK0001931.2E−265 Homo sapiens cDNA FLJ20186 fis, clone COLF0428 3697RG:207777:10007:B11 MA156:B11 X04714 gi|28779|emb|X04714.1HSAPOB10  1E−300 Human mRNA for apolipoprotein B-100 (apoB-100) 3698RG:221172:10007:C11 MA156:C11 M14333 gi|181171|gb|M14333.1HUMCSYNA2.2E−97 Homo sapiens c-syn protooncogene mRNA, complete cds 3699I:1968436:16B02:C05 MA90:C05 0.33281 3700 I:2060973:16A02:G11 MA88:G11AB035384 gi|7619897|dbj|AB035384.1AB035384 2.6E−291 Homo sapiens mRNAfor SRp25 nuclear protein, complete cds 3701 RG:1369494:10013:B05MA162:B05 AF008552 gi|2979629|gb|AF008552.1AF008552   1E−300 Homosapiens aurora-related kinase 2 (ARK2) mRNA, complete cds 3702RG:1752177:10015:E05 MA164:E05 3703 RG:1519327:10013:F05 MA162:F05X66364 gi|36620|emb|X66364.1HSSTHPKE 0 H. sapiens mRNA PSSALRE forserine/threonine protein kinase 3704 RG:1694569:10015:A11 MA164:A11X06323 gi|34753|emb|X06323.1HSMRL3R Human 0 MRL3 mRNA for ribosomalprotein L3 homologue (MRL3 = mammalian ribosome L3) 3705RG:1839794:10015:E11 MA164:E11 U28387 gi|881950|gb|U28387.1HSU28387Human 5.2E−175 hexokinase II pseudogene, complete cds 3706I:514124:17A02:D05 MA92:D05 AJ420434 gi|17066298|emb|AJ420434.1HSA4204346.5E−114 Homo sapiens mRNA full length insert cDNA clone EUROIMAGE1499812 3707 I:997782:17A02:G05 MA92:G05 AB018346gi|3882326|dbj|AB018346.1AB018346 2.8E−185 Homo sapiens mRNA forKIAA0803 protein, partial cds 3708 I:1709364:09B02:F11 MA138:F11NM_018440 gi|16753228|ref|NM_018440.2 Homo 6.4E−180 sapiensphosphoprotein associated with glycosphingolipid-enriched microdomains(PAG), mRNA 3709 I:2004896:18A01:C06 MA95:C06 AK023512gi|10435467|dbj|AK023512.1AK023512   2E−117 Homo sapiens cDNA FLJ13450fis, clone PLACE1003027, highly similar to Homo sapiens mRNA for KIAA3710 RG:172982:10006:F06 MA155:F06 D83492 gi|2281007|dbj|D83492.1D83492Homo 0 sapiens mRNA for Eph-family protein, complete cds 3711RG:180978:10006:G06 MA155:G06 D83492 gi|2281007|dbj|D83492.1D83492 Homo0 sapiens mRNA for Eph-family protein, complete cds 3712RG:129528:10006:B12 MA155:B12 U00238 gi|404860|gb|U00238.1U00238 Homo1.6E−286 sapiens glutamine PRPP amidotransferase (GPAT) mRNA, completecds 3713 RG:186511:10006:G12 MA155:G12 AK000250gi|7020204|dbj|AK000250.1AK000250 3.4E−204 Homo sapiens cDNA FLJ20243fis, clone COLF6418, highly similar to NUCL_HUMAN NUCLEOLIN 3714I:2005910:16B01:B06 MA89:B06 AJ340058gi|15884476|emb|AJ340058.1HSA340058 2.8E−110 Homo sapiens genomicsequence surrounding NotI site, clone NR5-ID23C 3715 I:620871:16A01:D06MA87:D06 BC007422 gi|13938544|gb|BC007422.1BC007422 3.5E−250 Homosapiens, acid phosphatase 1, soluble, clone MGC: 3499 IMAGE: 3027769,mRNA, complete cds 3716 I:1920819:16A01:A12 MA87:A12 BC015123gi|15929378|gb|BC015123.1BC015123 8.2E−276 Homo sapiens, Similar toretinoblastoma- binding protein 4, clone IMAGE: 3686783, mRNA, partialcds 3717 I:990375:16A01:E12 MA87:E12 M10050gi|182355|gb|M10050.1HUMFABPL 1.8E−267 Human liver fatty acid bindingprotein (FABP) mRNA, complete cds 3718 I:690313:16A01:G12 MA87:G12BC017201 gi|16877960|gb|BC017201.1BC017201 3.8E−200 Homo sapiens,insulin-like growth factor binding protein 7, clone MGC: 3699 IMAGE:3632247, mRNA, c 3719 RG:878195:10012:A06 MA161:A06 M83653gi|179635|gb|M83653.1HUMC1PHTYR 0 Homo sapiens cytoplasmicphosphotyrosyl protein phosphatase (clone type 1) complete cds 3720RG:687128:10010:D06 MA159:D06 S75546 gi|914097|gb|S75546.1S75546 protein1.7E−38 kinase PRK1 [human, fetal brain, mRNA, 3001 nt] 3721I:884855:17B01:D06 MA93:D06 AK055393 gi|16550110|dbj|AK055393.1AK055393  4E−228 Homo sapiens cDNA FLJ30831 fis, clone FEBRA2001989 3722I:1218621:17B01:F06 MA93:F06 3723 I:620371:17A01:H06 MA91:H06 BC016472gi|16741273|gb|BC016472.1BC016472   1E−203 Homo sapiens, clone MGC:17244 IMAGE: 4178911, mRNA, complete cds 3724 I:1681610:09B01:D06MA137:D06 AK055827 gi|16550653|dbj|AK055827.1AK055827 1.3E−124 Homosapiens cDNA FLJ31265 fis, clone KIDNE2006030, moderately similar toGallus gallus syndesmo 3725 RG:265206:10007:G06 MA156:G06 U25975gi|984304|gb|U25975.1HSU25975 Human   1E−231 serine kinase (hPAK65)mRNA, partial cds 3726 RG:268073:10007:H06 MA156:H06 AF226044gi|9295326|gb|AF226044.1AF226044 9.8E−118 Homo sapiens HSNFRK (HSNFRK)mRNA, complete cds 3727 I:2117221:16A02:F06 MA88:F06 0.22151 AF130089gi|11493482|gb|AF130089.1AF130089 9.5E−152 Homo sapiens clone FLB9440PRO2550 mRNA, complete cds 3728 I:1760693:16B02:G06 MA90:G06 3729I:776793:16B02:B12 MA90:B12 AF086524 gi|3483869|gb|AF086524.1HUMZE04F101.5E−283 Homo sapiens full length insert cDNA clone ZE04F10 3730RG:1405692:10013:C06 MA162:C06 X60489 gi|31099|emb|X60489.1HSEF1B Human0 mRNA for elongation factor-1-beta 3731 RG:1707747:10015:B12 MA164:B12M29536 gi|182066|gb|M29536.1HUMELF2 Human 0 translational initiationfactor 2 beta subunit (elF-2-beta) mRNA, complete cds 3732RG:1722789:10015:C12 MA164:C12 AF183421 gi|9963780|gb|AF183421.1AF1834210 Homo sapiens small GTP-binding protein rab22b mRNA, complete cds 3733I:2112348:17B02:E06 MA94:E06 AK026529 gi|10439407|dbj|AK026529.1AK0265291.7E−196 Homo sapiens cDNA: FLJ22876 fis, clone KAT02954, highly similarto AF056183 Homo sapiens WS beta 3734 I:630458:17A02:F06 MA92:F06AK025537 gi|10438082|dbj|AK025537.1AK025537 7.2E−211 Homo sapiens cDNA:FLJ21884 fis, clone HEP02863 3735 I:901577:17A02:H06 MA92:H06 AK000771gi|7021067|dbj|AK000771.1AK000771 2.3E−195 Homo sapiens cDNA FLJ20764fis, clone COL08503 3736 I:2298081:17B02:E12 MA94:E12 AL080169gi|5262637|emb|AL080169.1HSM800688 0 Homo sapiens mRNA; cDNADKFZp434C171 (from clone DKFZp434C171); partial cds 3737I:2718565:09B02:H12 MA138:H12 AF207600 gi|9998951|gb|AF207600.2AF2076003.2E−253 Homo sapiens ethanolamine kinase (EKI1) mRNA, complete cds 3738M00056237C:E03 MA181:A01 0.8773 U27317 gi|9989705|gb|U27317.2HSHSD11K17.9E−23 Homo sapiens 11 beta-hydroxysteroid dehydrogenase 2 (HSD11B2)gene, complete cds 3739 M00055261C:F04 MA197:E01 NM_033643gi|16117795|ref|NM_033643.1 Homo 8.3E−223 sapiens ribosomal protein L36(RPL36), transcript variant 1, mRNA 3740 M00055353D:A04 MA197:D07BC006794 gi|13905021|gb|BC006794.1BC006794 1.1E−156 Homo sapiens,Similar to interferon induced transmembrane protein 3 (1-8U), clone MGC:5225 IMAGE: 3741 M00055357B:B10 MA197:H07 BC006794gi|13905021|gb|BC006794.1BC006794   3E−275 Homo sapiens, Similar tointerferon induced transmembrane protein 3 (1-8U), clone MGC: 5225IMAGE: 3742 M00056386D:H12 MA173:C01 BC007700gi|14712760|gb|BC007700.1BC007700 6.1E−180 Homo sapiens, clone IMAGE:3954272, mRNA 3743 M00056394B:B04 MA173:D01 BC006791gi|13905015|gb|BC006791.1BC006791   1E−175 Homo sapiens, ribosomalprotein L10a, clone MGC: 5203 IMAGE: 2901249, mRNA, complete cds 3744M00056395A:B04 MA173:E01 BC016835 gi|16877126|gb|BC016835.1BC0168354.2E−55 Homo sapiens, Similar to synaptophysin- like protein, clone MGC:10011 IMAGE: 3883697, mRNA, complet 3745 M00056396B:G05 MA173:F01AK026171 gi|10438934|dbj|AK026171.1AK026171 2.9E−94 Homo sapiens cDNA:FLJ22518 fis, clone HRC12216, highly similar to AF151069 Homo sapiensHSPC235 3746 M00056137A:A05 MA180:G01 3747 M00056401C:C03 MA173:H01L20688 gi|404044|gb|L20688.1HUMLYGDI 6.4E−267 Human GDP-dissociationinhibitor protein (Ly-GDI) mRNA, complete cds 3748 M00056484A:F06MA173:E07 NM_003145 gi|6552341|ref|NM_003145.2 Homo 1.3E−252 sapienssignal sequence receptor, beta (translocon-associated protein beta)(SSR2), mRNA 3749 M00056193B:C11 MA180:F07 AF119905gi|7770246|gb|AF119905.1AF119905 4.6E−193 Homo sapiens PRO2853 mRNA,complete cds 3750 M00056484B:B07 MA173:G07 AF203815gi|6979641|gb|AF203815.1AF203815 6.6E−214 Homo sapiens alpha genesequence 3751 M00056193B:D06 MA180:G07 AF004162gi|3046385|gb|AF004162.1AF004162 8.3E−201 Homo sapiens nickel-specificinduction protein (Cap43) mRNA, complete cds 3752 M00056194B:G06MA180:H07 BC016834 gi|16877123|gb|BC016834.1BC016834 2.5E−294 Homosapiens, clone IMAGE: 3883264, mRNA, partial cds 3753 M00054633D:B07MA187:A01 BC018210 gi|17390469|gb|BC018210.1BC018210 7.9E−279 Homosapiens, tubulin-specific chaperone a, clone MGC: 9129 IMAGE: 3861138,mRNA, complete cds 3754 M00054633D:E06 MA187:B01 X52003gi|311379|emb|X52003.1HSPS2MKN   3E−275 H. sapiens pS2 protein gene 3755M00054848A:C03 MA189:H01 NM_001010 gi|17158043|ref|NM_001010.2 Homo3.6E−287 sapiens ribosomal protein S6 (RPS6), mRNA 3756 M00054882C:C06MA189:A07 BC000915 gi|14705283|gb|BC000915.2BC000915 5.3E−283 Homosapiens, PDZ and LIM domain 1 (elfin), clone MGC: 5344 IMAGE: 2985229,mRNA, complete cds 3757 M00054678D:A03 MA187:C07 BC015564gi|15990405|gb|BC015564.1BC015564 7.8E−279 Homo sapiens, cold shockdomain protein A, clone MGC: 12695 IMAGE: 4137643, mRNA, complete cds3758 M00054679B:B03 MA187:D07 BC015642 gi|15990506|gb|BC015642.1BC0156424.8E−277 Homo sapiens, Similar to serine (or cysteine) proteinaseinhibitor, clade A (alpha-1 antiproteina 3759 M00054680B:D06 MA187:G07BC009623 gi|16307089|gb|BC009623.1BC009623 8.4E−279 Homo sapiens,Similar to nucleophosmin (nucleolar phosphoprotein B23, numatrin), cloneMGC: 17308 3760 M00054680C:A06 MA187:H07 U28387gi|881950|gb|U28387.1HSU28387 Human   9E−83 hexokinase II pseudogene,complete cds 3761 M00057176B:F11 MA193:B01 BC000419gi|12653300|gb|BC000419.1BC000419 1.1E−296 Homo sapiens, catechol-O-methyltransferase, clone MGC: 8663 IMAGE: 2964400, mRNA, complete cds3762 M00057181A:D01 MA193:C01 AY008283 gi|15192138|gb|AY008283.1 Homo4.9E−196 sapiens porimin mRNA, complete cds 3763 M00057219D:B04MA193:D07 NM_001015 gi|14277698|ref|NM_001015.2 Homo 3.4E−175 sapiensribosomal protein S11 (RPS11), mRNA 3764 M00042341A:D12 MA167:A01NM_002153 gi|4504502|ref|NM_002153.1 Homo 8.3E−123 sapienshydroxysteroid (17-beta) dehydrogenase 2 (HSD17B2), mRNA 3765M00042433B:G09 MA171:B01 AJ295637 gi|9581767|emb|AJ295637.1HSA2956371.2E−221 Homo sapiens mRNA for URIM protein 3766 M00042435A:F08MA171:D01 BC014048 gi|15559357|gb|BC014048.1BC014048 4.6E−122 Homosapiens, clone IMAGE: 3348134, mRNA, partial cds 3767 M00042437B:G03MA171:E01 X59315 gi|33247|emb|X59315.1HSIGKL012 1.5E−119 H. sapiens genefor Ig kappa light chain variable region “012” 3768 M00042525D:E07MA167:F01 BC005982 gi|13543665|gb|BC005982.1BC005982 1.4E−105 Homosapiens, peptidylprolyl isomerase A (cyclophilin A), clone MGC: 14681IMAGE: 4109260, mRNA, co 3769 M00042438B:D01 MA171:F01 NM_004063gi|16507959|ref|NM_004063.2 Homo 6.1E−264 sapiens cadherin 17, LIcadherin (liver- intestine) (CDH17), mRNA 3770 M00042529C:G07 MA167:G01L02785 gi|291963|gb|L02785.1HUMDRA Homo 5.8E−261 sapiens colonmucosa-associated (DRA) mRNA, complete cds 3771 M00042529D:B12 MA167:H010.07368 BC007011 gi|13937818|gb|BC007011.1BC007011 2.1E−145 Homosapiens, clone MGC: 12335 IMAGE: 3686576, mRNA, complete cds 3772M00042700A:E05 MA167:A07 U07550 gi|469170|gb|U07550.1HSU07550 Human4.1E−212 chaperonin 10 mRNA, complete cds 3773 M00042777D:G05 MA171:B07AY007243 gi|12621025|gb|AY007243.1 Homo 6.1E−264 sapiens regeneratinggene type IV mRNA, complete cds 3774 M00042781C:F03 MA171:D07 BC016753gi|16876954|gb|BC016753.1BC016753 3.7E−259 Homo sapiens, clone MGC: 1138IMAGE: 2987963, mRNA, complete cds 3775 M00042783C:F10 MA171:E07 0.803663776 M00042702D:B02 MA167:F07 AJ010446gi|3954892|emb|AJ010446.1HSA010446 2.8E−154 Homo sapiens mRNA forimmunoglobulin kappa light chain, anti-RhD, therad 24 3777M00042785B:F11 MA171:H07 AF254415 gi|13897565|gb|AF254415.1AF2544153.9E−209 Homo sapiens gastrointestinal secretory protein GISP mRNA,complete cds 3778 M00056566C:C03 MA174:A07 NM_031901gi|16950594|ref|NM_031901.2 Homo 1.4E−255 sapiens mitochondrialribosomal protein S21 (MRPS21), transcript variant 1, nuclear geneencoding 3779 M00056567B:A09 MA174:C07 BC000396gi|12653254|gb|BC000396.1BC000396   1E−293 Homo sapiens,ubiquitin-conjugating enzyme E2N (homologous to yeast UBC13), clone MGC:8489 IMAGE: 3780 M00056569B:D09 MA174:G07 U61267gi|1418285|gb|U61267.1HSU61267 Homo 4.4E−243 sapiens putative splicefactor transformer2- beta mRNA, complete cds 3781 M00056571D:E05MA174:H07 BC017696 gi|17389285|gb|BC017696.1BC017696 6.6E−239 Homosapiens, Similar to RIKEN cDNA 2410075D05 gene, clone MGC: 21057 IMAGE:4393374, mRNA, complet 3782 RG:376801:10009:C01 MA158:C01 AB017642gi|4519628|dbj|AB017642.1AB017642 8.9E−282 Homo sapiens mRNA foroxidative-stress responsive 1, complete cds 3783 RG:365436:10009:B07MA158:B07 AK022055 gi|10433374|dbj|AK022055.1AK022055 1.1E−290 Homosapiens cDNA FLJ11993 fis, clone HEMBB1001429, highly similar to Homosapiens leucine amino 3784 RG:416839:10009:D07 MA158:D07 AK026432gi|10439295|dbj|AK026432.1AK026432 0 Homo sapiens cDNA: FLJ22779 fis,clone KAIA1741 3785 RG:784224:10011:E07 MA160:E07 L03840gi|182570|gb|L03840.1HUMFGFR4X 7.3E−258 Human fibroblast growth factorreceptor 4 (FGFR4) mRNA, complete cds 3786 RG:796852:10011:G07 MA160:G07AF087909 gi|10121889|gb|AF087909.1AF087909 4.4E−271 Homo sapiensNIMA-related kinase 6 (NEK6) mRNA, complete cds 3787 M00043412A:F04MA184:E01 NM_000993 gi|15812219|ref|NM_000993.2 Homo 8.3E−158 sapiensribosomal protein L31 (RPL31), mRNA 3788 M00057273B:H10 MA182:H01AB042820 gi|11041627|dbj|AB042820.1AB042820 5.6E−41 Homo sapiens RPL6gene for ribosomal protein L6, complete cds 3789 M00054506C:B10MA184:B07 NM_001012 gi|4506742|ref|NM_001012.1 Homo 2.6E−185 sapiensribosomal protein S8 (RPS8), mRNA 3790 M00054507D:G03 MA184:F07 U19765gi|790570|gb|U19765.1HSU19765 Human 1.5E−221 nucleic acid bindingprotein gene, complete cds 3791 M00054935B:B03 MA198:E01 0.06563NM_001644 gi|5921993|ref|NM_001644.2 Homo 1.2E−128 sapiensapolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1),transcript variant 3792 M00054935D:C11 MA198:H01 NM_002026gi|16933541|ref|NM_002026.1 Homo 1.1E−190 sapiens fibronectin 1 (FN1),transcript variant 1, mRNA 3793 M00054976A:E09 MA198:D07 BC017189gi|16877928|gb|BC017189.1BC017189 2.7E−188 Homo sapiens, myo-inositol1-phosphate synthase A1, clone MGC: 726 IMAGE: 3140452, mRNA, complete c3794 M00055788B:F08 MA170:C07 V00662 gi|13003|emb|V00662.1MIHSXX1.3E−165 H. sapiens mitochondrial genome 3795 M00055791A:E10 MA170:G07X01117 gi|57149|emb|X01117.1RNRRNA06 Rat   7E−92 18S rRNA sequence 3796M00055224C:H11 MA196:E07 BC008952 gi|14286301|gb|BC008952.1BC008952  5E−171 Homo sapiens, lactate dehydrogenase B, clone MGC: 3600 IMAGE:3028947, mRNA, complete cds 3797 M00055932A:C02 MA179:B01 BC019362gi|17939458|gb|BC019362.1BC019362 2.1E−226 Homo sapiens, guaninenucleotide binding protein (G protein), beta polypeptide 2-like 1, cloneMG 3798 M00056908A:F12 MA177:C01 0.86486 3799 M00055935D:B06 MA179:D01D17041 gi|598766|dbj|D17041.1HUMD3F06M5 3.3E−182 Human HepG2 partialcDNA, clone hmd3f06m5 3800 M00056908D:D08 MA177:E01 AK026649gi|10439547|dbj|AK026649.1AK026649 2.3E−154 Homo sapiens cDNA: FLJ22996fis, clone KAT11938 3801 M00055942B:F08 MA179:F01 X98311gi|1524059|emb|X98311.1HSCGM2ANT 5.9E−196 H. sapiens mRNA forcarcinoembryonic antigen family member 2, CGM2 3802 M00056910A:B07MA177:G01 BC009599 gi|16307042|gb|BC009599.1BC009599 8.3E−254 Homosapiens, clone MGC: 14690 IMAGE: 4134557, mRNA, complete cds 3803M00056952B:C08 MA177:H07 Z85181 gi|1834892|emb|Z85181.1HSZ85181   8E−186H. sapiens Ig lambda light chain variable region gene (6-09OIIA61)rearranged; Ig- Light-Lambda; VLam 3804 M00054728C:E03 MA188:A01 M34664gi|184411|gb|M34664.1HUMHSP60A 1.3E−283 Human chaperonin (HSP60) mRNA,complete cds 3805 M00054728D:E06 MA188:B01 X16064gi|37495|emb|X16064.1HSTUMP Human   1E−300 mRNA for translationallycontrolled tumor protein 3806 M00054731C:H01 MA188:H01 X73502gi|406853|emb|X73502.1HSENCY20 H. sapiens 1.9E−267 mRNA for cytokeratin20 3807 M00054778B:A12 MA188:D07 AJ276249gi|7362984|emb|AJ276249.1HSA276249   2E−91 Homo sapiens partial mRNA,clone c1- 10e16 3808 M00054778C:D08 MA188:F07 NM_002137gi|14043073|ref|NM_002137.2 Homo 1.8E−34 sapiens heterogeneous nuclearribonucleoprotein A2/B1 (HNRPA2B1), transcript variant A2, mRNA 3809M00054780A:G06 MA188:H07 BC000035 gi|12652584|gb|BC000035.1BC0000353.6E−287 Homo sapiens, CGI-89 protein, clone MGC: 845 IMAGE: 3506601,mRNA, complete cds 3810 M00042899D:D02 MA168:A01 Y00339gi|29586|emb|Y00339.1HSCA2 Human 1.5E−233 mRNA for carbonic anhydrase II(EC 4.2.1.1) 3811 M00042831B:G10 MA172:C01 AK024740gi|10437104|dbj|AK024740.1AK024740 6.2E−264 Homo sapiens cDNA: FLJ21087fis, clone CAS03323 3812 M00042833A:G07 MA172:D01 AF047470gi|2906145|gb|AF047470.1AF047470   3E−166 Homo sapiens malatedehydrogenase precursor (MDH) mRNA, nuclear gene encoding mitochondrialprotei 3813 M00042906D:F05 MA168:E01 L31792gi|471076|gb|L31792.1HUMCGM2A 1.1E−200 Homo sapiens carcinoembryonicantigen (CGM2) mRNA, complete cds 3814 M00042910C:A02 MA168:G01 AF113700gi|6855634|gb|AF113700.1AF113700 7.6E−245 Homo sapiens clone FLB97373815 M00042838C:D06 MA172:H01 AK026558gi|10439440|dbj|AK026558.1AK026558 1.7E−214 Homo sapiens cDNA: FLJ22905fis, clone KAT05654, highly similar to HUMRPL18A Homo sapiens riboso3816 M00042867B:F03 MA172:A07 0.30983 D87666gi|1620016|dbj|D87666.1D87666 Human 1.3E−101 heart mRNA for heat shockprotein 90, partial cds 3817 M00055439B:G05 MA168:B07 AY029066gi|14017398|gb|AY029066.1 Homo 9.6E−263 sapiens Humanin (HN1) mRNA,complete cds 3818 M00055442D:E12 MA168:F07 BC005354gi|13529169|gb|BC005354.1BC005354 6.6E−239 Homo sapiens, ribosomalprotein, large P2, clone MGC: 12453 IMAGE: 4052568, mRNA, complete cds3819 M00056711D:A02 MA175:B01 Z11566 gi|1066270|emb|Z11566.1HSPR22MR6.7E−133 H. sapiens mRNA for Pr22 protein 3820 M00056771C:A12 MA175:A07X02152 gi|34312|emb|X02152.1HSLDHAR   6E−130 Human mRNA for lactatedehydrogenase- A (LDH-A, EC 1.1.1.27) 3821 M00056772D:G07 MA175:C07NM_001016 gi|14277699|ref|NM_001016.2 Homo 1.2E−218 sapiens ribosomalprotein S12 (RPS12), mRNA 3822 M00056782D:E04 MA175:F07 AF346968gi|13272626|gb|AF346968.1AF346968 3.6E−172 Homo sapiens mitochondrion,complete genome 3823 M00056785D:G01 MA175:G07 NM_001019gi|14165468|ref|NM_001019.2 Homo 1.5E−230 sapiens ribosomal protein S15a(RPS15A), mRNA 3824 M00056788C:A01 MA175:H07 AY029066gi|14017398|gb|AY029066.1 Homo 3.5E−287 sapiens Humanin (HN1) mRNA,complete cds 3825 RG:1663880:10014:F07 MA163:F07 BC019315gi|17939511|gb|BC019315.1BC019315   1E−300 Homo sapiens,N-acetylneuraminic acid phosphate synthase; sialic acid synthase, cloneMGC: 4339 IM 3826 M00043310B:D08 MA183:C01 NM_000969gi|14591908|ref|NM_000969.2 Homo 1.5E−261 sapiens ribosomal protein L5(RPL5), mRNA 3827 M00054538C:G03 MA185:C01 BC000734gi|12653884|gb|BC000734.1BC000734   4E−234 Homo sapiens, eukaryotictranslation initiation factor 3, subunit 6 (48 kD), clone MGC: 2060IMAGE: 3828 M00043315C:G05 MA183:H01 AK023362gi|10435266|dbj|AK023362.1AK023362 2.7E−241 Homo sapiens cDNA FLJ13300fis, clone OVARC1001342, highly similar to 40S RIBOSOMAL PROTEIN S8 3829M00055397B:E08 MA199:B01 X06747 gi|36101|emb|X06747.1HSRNPA1 Human9.7E−132 hnRNP core protein A1 3830 M00056624B:H11 MA186:C01 X56597gi|31394|emb|X56597.1HSFIB Human 7.7E−192 humFib mRNA for fibrillarin3831 M00055423C:C03 MA199:E07 L01124 gi|307390|gb|L01124.1HUMRPS13A9.1E−154 Human ribosomal protein S13 (RPS13) mRNA, complete cds 3832M00056668D:C06 MA186:F07 BC013231 gi|15301504|gb|BC013231.1BC0132319.8E−263 Homo sapiens, clone IMAGE: 3462987, mRNA 3833 M00056669B:A10MA186:G07 NM_001025 gi|14790142|ref|NM_001025.2 Homo 3.7E−290 sapiensribosomal protein S23 (RPS23), mRNA 3834 M00055424A:D01 MA199:G07BC002362 gi|12803116|gb|BC002362.1BC002362 6.4E−183 Homo sapiens,lactate dehydrogenase B, clone MGC: 8627 IMAGE: 2961445, mRNA, completecds 3835 M00056669B:E07 MA186:H07 NM_002295 gi|9845501|ref|NM_002295.2Homo 9.1E−232 sapiens laminin receptor 1 (67 kD, ribosomal protein SA)(LAMR1), mRNA 3836 M00055424D:F01 MA199:H07 NM_001012gi|4506742|ref|NM_001012.1 Homo 4.4E−190 sapiens ribosomal protein S8(RPS8), mRNA 3837 M00056243A:H07 MA181:C02 0.86405 3838 M00056243C:G10MA181:D02 0.46512 3839 M00055528D:H03 MA169:F02 0.6783 3840M00055607B:A11 MA169:B08 AF161415 gi|6841243|gb|AF161415.1AF1614153.5E−253 Homo sapiens HSPC297 mRNA, partial cds 3841 M00055363C:E02MA197:A08 0.62737 3842 M00055373D:H02 MA197:F08 BC013016gi|15278200|gb|BC013016.1BC013016 3.3E−125 Homo sapiens, Similar toribosomal protein L19, clone MGC: 4526 IMAGE: 3010178, mRNA, completecds 3843 M00055374D:E01 MA197:H08 NM_000979 gi|15431298|ref|NM_000979.2Homo 1.5E−261 sapiens ribosomal protein L18 (RPL18), mRNA 3844M00056401D:D09 MA173:A02 BC008492 gi|14250147|gb|BC008492.1BC0084921.6E−105 Homo sapiens, ribosomal protein L3, clone MGC: 14821 IMAGE:4251511, mRNA, complete cds 3845 M00056139D:A10 MA180:B02 X16356gi|37203|emb|X16356.1HSTM3CEA 3.9E−237 Human mRNA for transmembranecarcinoembryonic antigen BGPC (part.) (formerly TM3-CEA) 3846M00056140A:E11 MA180:D02 U96628 gi|2343084|gb|U96628.1HSU96628 Homo2.4E−182 sapiens nuclear antigen H731-like protein mRNA, complete cds3847 M00056142D:A08 MA180:E02 BC015958 gi|16358989|gb|BC015958.1BC0159584.2E−268 Homo sapiens, clone MGC: 15290 IMAGE: 3940309, mRNA, completecds 3848 M00056412D:A09 MA173:F02 0.85039 3849 M00056142D:H11 MA180:F02AK025078 gi|10437520|dbj|AK025078.1AK025078 3.8E−120 Homo sapiens cDNA:FLJ21425 fis, clone COL04162 3850 M00056414C:F03 MA173:G02 M29548gi|181966|gb|M29548.1HUMEF1AB 1.7E−114 Human elongation factor 1-alpha(EF1A) mRNA, partial cds 3851 M00056196A:H09 MA180:B08 D84239gi|1944351|dbj|D84239.1D84239 Homo   2E−251 sapiens mRNA for IgG Fcbinding protein, complete cds 3852 M00056200A:E11 MA180:D08 U14528gi|549987|gb|U14528.1HSU14528 Human 4.3E−299 sulfate transporter (DTD)mRNA, complete cds 3853 M00056488C:G01 MA173:E08 L08048gi|184250|gb|L08048.1HUMHMG1C 3.3E−281 Human non-histone chromosomalprotein (HMG-1) retropseudogene 3854 M00056200B:B01 MA180:E08 D84239gi|1944351|dbj|D84239.1D84239 Homo 1.5E−233 sapiens mRNA for IgG Fcbinding protein, complete cds 3855 M00056203B:G08 MA180:F08 0.89391 3856M00056493A:F09 MA173:H08 X14831 gi|37199|emb|X14831.1HSTM2CEA 4.2E−115Human mRNA for transmembrane carcinoembryonic antigen BGPb (formerlyTM2-CEA) 3857 M00054640D:D12 MA187:B02 0.89884 3858 M00054643B:F04MA187:D02 0.66848 3859 M00054643C:D08 MA187:E02 BC000491gi|12653440|gb|BC000491.1BC000491 1.6E−236 Homo sapiens, proliferatingcell nuclear antigen, clone MGC: 8367 IMAGE: 2820036, mRNA, complete cd3860 M00054854D:B06 MA189:F02 M16660 gi|184420|gb|M16660.1HUMHSP902.4E−263 Human 90-kDa heat-shock protein gene, cDNA, complete cds 3861M00054644B:F02 MA187:G02 BC017414 gi|16924273|gb|BC017414.1BC0174141.2E−246 Homo sapiens, Similar to signal recognition particle 9 kD,clone IMAGE: 4655251, mRNA, partial cds 3862 M00054857A:E08 MA189:G02BC016753 gi|16876954|gb|BC016753.1BC016753 8.6E−229 Homo sapiens, cloneMGC: 1138 IMAGE: 2987963, mRNA, complete cds 3863 M00054681D:G03MA187:B08 BC019360 gi|17939583|gb|BC019360.1BC019360   1E−300 Homosapiens, clone IMAGE: 4025624, mRNA 3864 M00054682D:F11 MA187:D080.13542 AF116637 gi|7959775|gb|AF116637.1AF116637 3.2E−210 Homo sapiensPRO1489 mRNA, complete cds 3865 M00054684B:C07 MA187:F08 BC001781gi|12804704|gb|BC001781.1BC001781 8.6E−176 Homo sapiens, ribosomalprotein L44, clone MGC: 2064 IMAGE: 3353669, mRNA, complete cds 3866M00057191B:E11 MA193:D02 AK026528 gi|10439405|dbj|AK026528.1AK0265284.6E−274 Homo sapiens cDNA: FLJ22875 fis, clone KAT02879 3867M00057194B:G12 MA193:G02 AF228422 gi|12656020|gb|AF228422.1AF2284221.9E−117 Homo sapiens normal mucosa of esophagus specific 1 (NMES1)mRNA, complete cds 3868 M00057222D:G09 MA193:B08 D49400gi|1395161|dbj|D49400.1HUMVATPASE 3.9E−262 Homo sapiens mRNA forvacuolar ATPase, complete cds 3869 M00042531B:H03 MA167:A02 M15042gi|180198|gb|M15042.1HUMCEA Human 6.3E−211 carcinoembryonic antigen mRNA3870 M00042440C:G04 MA171:A02 0.89441 3871 M00042533C:D02 MA167:C02X56999 gi|37568|emb|X56999.1HSUBA52P 3.7E−29 Human UbA52 placental mRNAfor ubiquitin-52 amino acid fusion protein 3872 M00042536D:H05 MA167:E02AF146019 gi|10197599|gb|AF146019.1AF146019   3E−26 Homo sapienshepatocellular carcinoma antigen gene 520 mRNA, complete cds 3873M00042465B:E04 MA171:E02 BC016732 gi|16876903|gb|BC016732.1BC0167325.7E−202 Homo sapiens, thymosin, beta 4, X chromosome, clone MGC: 24503IMAGE: 4096207, mRNA, complete cds 3874 M00042537D:F10 MA167:F02BC000889 gi|12654142|gb|BC000889.1BC000889 1.6E−236 Homo sapiens, RNApolymerase I 16 kDa subunit, clone MGC: 4881 IMAGE: 3462906, mRNA,complete cds 3875 M00042467B:B04 MA171:F02 V00572gi|35434|emb|V00572.1HSPGK1 Human   1E−240 mRNA encodingphosphoglycerate kinase 3876 M00042538D:D12 MA167:G02 X68195gi|36165|emb|X68195.1HSRSPAC 6.6E−24 H. sapiens genomic DNA of ribosomalRNA intergenic spacer sequence 3877 M00042467B:B08 MA171:G02 U11861gi|515482|gb|U11861.1HSU11861 Human 1.7E−165 G10 homolog (edg-2) mRNA,complete cds 3878 M00042711B:G09 MA167:B08 AF130094gi|11493492|gb|AF130094.1AF130094   3E−207 Homo sapiens clone FLC0165mRNA sequence 3879 M00042790B:E12 MA171:B08 AF039400gi|4009457|gb|AF039400.1AF039400 5.9E−261 Homo sapiens calcium-dependentchloride channel-1 (hCLCA1) mRNA, complete cds 3880 M00042791A:C10MA171:C08 NM_000147 gi|4503802|ref|NM_000147.1 Homo 1.3E−252 sapiensfucosidase, alpha-L-1, tissue (FUCA1), mRNA 3881 M00042711C:H05MA167:D08 X16354 gi|37197|emb|X16354.1HSTM1CEA 2.7E−163 Human mRNA fortransmembrane carcinoembryonic antigen BGPa (formerly TM1-CEA) 3882M00042801D:B02 MA171:H08 BC002348 gi|12803088|gb|BC002348.1BC0023484.9E−196 Homo sapiens, nuclear transport factor 2 (placental protein15), clone MGC: 8327 IMAGE: 2819267, mR 3883 M00042801D:B02 MA171:H08BC002348 gi|12803088|gb|BC002348.1BC002348 4.9E−196 Homo sapiens,nuclear transport factor 2 (placental protein 15), clone MGC: 8327IMAGE: 2819267, mR 3884 M00056532A:D09 MA174:C02 0.78082 3885M00056533D:H04 MA174:E02 AK000070 gi|7019918|dbj|AK000070.1AK0000703.6E−287 Homo sapiens cDNA FLJ20063 fis, clone COL01524 3886M00056575B:C04 MA174:B08 AK000113 gi|7019989|dbj|AK000113.1AK0001132.4E−263 Homo sapiens cDNA FLJ20106 fis, clone COL04830 3887M00056578C:A09 MA174:C08 NM_000988 gi|17017972|ref|NM_000988.2 Homo2.1E−198 sapiens ribosomal protein L27 (RPL27), mRNA 3888RG:1862072:20001:D08 MA139:D08 X61633 gi|37957|emb|X61633.1HSWIGEEX49.2E−25 H. sapiens Wilms tumor gene 1, exon 4 3889 RG:1862465:20001:F08MA139:F08 0.81221 3890 RG:347381:10009:A02 MA158:A02 U38846gi|1200183|gb|U38846.1HSU38846 0 Human stimulator of TAR RNA binding(SRB) mRNA, complete cds 3891 RG:417093:10009:D08 MA158:D08 0.08361M17885 gi|190231|gb|M17885.1HUMPPARP0 4.4E−216 Human acidic ribosomalphosphoprotein P0 mRNA, complete cds 3892 M00043413B:C04 MA184:A02AK027437 gi|14042109|dbj|AK027437.1AK027437 5.2E−174 Homo sapiens cDNAFLJ14531 fis, clone NT2RM2000371, weakly similar to POLYRIBONUCLEOTIDENUCLEOT 3893 M00043502D:C12 MA184:F02 BC000820gi|12654032|gb|BC000820.1BC000820 5.2E−252 Homo sapiens, menage a trois1 (CAK assembly factor), clone MGC: 5154 IMAGE: 3453943, mRNA, complet3894 M00057341B:B11 MA182:E08 BC001955 gi|12805002|gb|BC001955.1BC0019551.1E−243 Homo sapiens, ribosomal protein S10, clone MGC: 4389 IMAGE:2905318, mRNA, complete cds 3895 M00054512A:F11 MA184:G08 0.19488 3896M00042353A:D05 MA182:H08 BC016352 gi|16741002|gb|BC016352.1BC016352  2E−123 Homo sapiens, small acidic protein, clone MGC: 24468 IMAGE:4082845, mRNA, complete cds 3897 M00054937B:D09 MA198:B02 S79979gi|1839333|gb|S79979.1S79979 ribosomal 2.8E−75 protein L37 [human, HeLacells, Genomic/mRNA, 754 nt] 3898 M00055797C:H09 MA170:D08 BC009699gi|16307220|gb|BC009699.1BC009699 8.2E−226 Homo sapiens, Similar to RNAhelicase- related protein, clone MGC: 9246 IMAGE: 3892441, mRNA, comple3899 M00055799B:C01 MA170:E08 X01117 gi|57149|emb|X01117.1RNRRNA06 Rat1.5E−51 18S rRNA sequence 3900 M00055194C:G12 MA196:D02 BC008062gi|14165518|gb|BC008062.1BC008062 7.7E−27 Homo sapiens, basictranscription factor 3, clone MGC: 2209 IMAGE: 2966788, mRNA, completecds 3901 M00055233B:D08 MA196:B08 0.55474 3902 M00055966C:D06 MA179:H023903 M00056024B:B06 MA179:D08 BC011949 gi|15080385|gb|BC011949.1BC011949  6E−261 Homo sapiens, Similar to carbonic anhydrase II, clone MGC: 9006IMAGE: 3863603, mRNA, complete cds 3904 M00056024C:G04 MA179:E08 3905M00054737D:F10 MA188:D02 BC018828 gi|17402971|gb|BC018828.1BC0188283.5E−284 Homo sapiens, clone IMAGE: 3343539, mRNA 3906 M00054780D:C09MA188:A08 BC007967 gi|14044092|gb|BC007967.1BC007967 2.2E−151 Homosapiens, clone MGC: 14460 IMAGE: 4304670, mRNA, complete cds 3907M00054787A:E09 MA188:D08 NM_006013 gi|15718685|ref|NM_006013.2 Homo  8E−279 sapiens ribosomal protein L10 (RPL10), mRNA 3908 M00054806B:E11MA188:E08 AK026650 gi|10439548|dbj|AK026650.1AK026650 1.3E−252 Homosapiens cDNA: FLJ22997 fis, clone KAT11962, highly similar to HSEF1ACHuman mRNA for elonga 3909 M00042913B:C11 MA168:B02 NM_000999gi|16306562|ref|NM_000999.2 Homo 2.4E−182 sapiens ribosomal protein L38(RPL38), mRNA 3910 M00042915B:B10 MA168:D02 AK058013gi|16554011|dbj|AK058013.1AK058013 2.2E−201 Homo sapiens cDNA FLJ25284fis, clone STM06787, highly similar to 15- HYDROXYPROSTAGLANDIN DEHYDR3911 M00054792C:E12 MA168:E02 D14530 gi|414348|dbj|D14530.1HUMRSPT4.1E−268 Human homolog of yeast ribosomal protein S28, complete cds 3912M00042842A:C01 MA172:G02 0.66829 3913 M00055450A:C09 MA168:H08 0.8 3914M00056804C:D01 MA175:H08 AF126743 gi|5052332|gb|AF126743.1AF1267433.1E−278 Homo sapiens DNAJ domain-containing protein MCJ (MCJ) mRNA,complete cds 3915 RG:1647954:10014:D08 MA163:D08 NM_001261gi|17017983|ref|NM_001261.2 Homo 1.9E−273 sapiens cyclin-dependentkinase 9 (CDC2- related kinase) (CDK9), mRNA 3916 RG:1664311:10014:F08MA163:F08 X02761 gi|31396|emb|X02761.1HSFIB1 Human 0 mRNA forfibronectin (FN precursor) 3917 RG:1671377:10014:G08 MA163:G08 BC013078gi|15341811|gb|BC013078.1BC013078 2.8E−297 Homo sapiens, clone MGC:17534 IMAGE: 3459415, mRNA, complete cds 3918 M00043316B:F10 MA183:C02X16064 gi|37495|emb|X16064.1HSTUMP Human 2.7E−269 mRNA fortranslationally controlled tumor protein 3919 M00054545B:A03 MA185:D02AF151048 gi|7106817|gb|AF151048.1AF151048 4.6E−271 Homo sapiens HSPC214mRNA, complete cds 3920 M00054545B:B09 MA185:E02 0.07415 X07979gi|31441|emb|X07979.1HSFNRB Human 1.2E−126 mRNA for integrin beta 1subunit 3921 M00054575A:B09 MA185:D08 X16064 gi|37495|emb|X16064.1HSTUMPHuman 3.2E−278 mRNA for translationally controlled tumor protein 3922M00043374B:H05 MA183:F08 0.11186 NM_053275 gi|16933545|ref|NM_053275.1Homo   3E−136 sapiens ribosomal protein, large, P0 (RPLP0), transcriptvariant 2, mRNA 3923 M00056641A:G11 MA186:F02 BC003352gi|13097158|gb|BC003352.1BC003352 3.6E−284 Homo sapiens, tumor protein,translationally-controlled 1, clone MGC: 5308 IMAGE: 2899964, mRNA, co3924 M00056642A:D08 MA186:H02 0.78693 3925 M00055403B:B11 MA199:H02NM_001021 gi|14591913|ref|NM_001021.2 Homo 5.8E−180 sapiens ribosomalprotein S17 (RPS17), mRNA 3926 M00056676B:C11 MA186:H08 AF346968gi|13272626|gb|AF346968.1AF346968 4.6E−165 Homo sapiens mitochondrion,complete genome 3927 M00055530D:B02 MA169:B03 NM_001012gi|4506742|ref|NM_001012.1 Homo 1.5E−261 sapiens ribosomal protein S8(RPS8), mRNA 3928 M00056253A:D06 MA181:C03 BC014166gi|15559610|gb|BC014166.1BC014166 1.2E−274 Homo sapiens, clone IMAGE:4549553, mRNA 3929 M00056253B:B06 MA181:D03 BC000053gi|12652614|gb|BC000053.1BC000053 1.7E−270 Homo sapiens, LPS-inducedTNF-alpha factor, clone IMAGE: 3506981, mRNA 3930 M00055642D:F09MA169:D09 AF203815 gi|6979641|gb|AF203815.1AF203815 2.2E−257 Homosapiens alpha gene sequence 3931 M00055643A:E09 MA169:E09 J03037gi|179771|gb|J03037.1HUMCAIIA Human   3E−247 carbonic anhydrase II mRNA,complete cds 3932 M00055643D:E02 MA169:F09 M10050gi|182355|gb|M10050.1HUMFABPL 2.1E−251 Human liver fatty acid bindingprotein (FABP) mRNA, complete cds 3933 M00055376D:D08 MA197:B09 D38112gi|644480|dbj|D38112.1HUMMTA Homo 8.5E−111 sapiens mitochondrial DNA,complete sequence 3934 M00056415C:D02 MA173:B03 0.67751 3935M00056146D:F05 MA180:B03 0.61693 3936 M00056417A:F02 MA173:C03 Z85099gi|1834810|emb|Z85099.1HSZ85099 2.7E−31 H. sapiens Ig lambda light chainvariable region gene (3-01OIIA11) rearranged; Ig- Light-Lambda; VLam3937 M00056148A:B07 MA180:C03 AK026170gi|10438933|dbj|AK026170.1AK026170 4.8E−134 Homo sapiens cDNA: FLJ22517fis, clone HRC12186 3938 M00056420C:E07 MA173:D03 BC010735gi|14789596|gb|BC010735.1BC010735 3.7E−262 Homo sapiens, Similar toeukaryotic translation elongation factor 1 alpha 1, clone MGC: 10096IMAG 3939 M00056150A:E04 MA180:D03 0.82941 3940 M00056421C:H11 MA173:F03X60489 gi|31099|emb|X60489.1HSEF1B Human 3.5E−228 mRNA for elongationfactor-1-beta 3941 M00056150C:A10 MA180:F03 AL360191gi|8919392|emb|AL360191.1HST000237 1.1E−237 Homo sapiens mRNA fulllength insert cDNA clone EUROIMAGE 781354 3942 M00056421D:H05 MA173:G03BC017338 gi|16878283|gb|BC017338.1BC017338 1.1E−159 Homo sapiens,fucosidase, alpha-L-1, tissue, clone MGC: 29579 IMAGE: 4871788, mRNA,complete cds 3943 M00056150C:C04 MA180:G03 AJ276249gi|7362984|emb|AJ276249.1HSA276249 1.3E−98 Homo sapiens partial mRNA,clone c1- 10e16 3944 M00056422B:D11 MA173:H03 BC001289gi|12654890|gb|BC001289.1BC001289 1.9E−120 Homo sapiens, Sjogrensyndrome antigen B (autoantigen La), clone MGC: 5194 IMAGE: 3454454,mRNA, co 3945 M00056151C:A12 MA180:H03 X59706gi|34204|emb|X59706.1HSLA1L1IG 1.5E−227 H. sapiens rearranged Humigla1L1gene encoding IgG light chain 3946 M00056493C:E06 MA173:A09 AF153608gi|5231140|gb|AF153608.1AF153608 1.3E−280 Homo sapiens sin3 associatedpolypeptide (SAP18) mRNA, complete cds 3947 M00056205D:E03 MA180:A090.78241 3948 M00056495A:G10 MA173:B09 M63573gi|337998|gb|M63573.1HUMSCYLP 4.5E−100 Human secreted cyclophilin-likeprotein (SCYLP) mRNA, complete cds 3949 M00056206D:B10 MA180:E09AF001893 gi|2529723|gb|AF001893.1BETA2 Human 1.1E−35 MEN1 region cloneepsilon/beta mRNA, 3′ fragment 3950 M00056501D:C08 MA173:H09 Y11339gi|7576275|emb|Y11339.2HSY11339 1.9E−220 Homo sapiens mRNA for GalNAcalpha-2, 6-sialyltransferase I, long form 3951 M00056209D:H10 MA180:H090.08151 J03037 gi|179771|gb|J03037.1HUMCAIIA Human 1.6E−258 carbonicanhydrase II mRNA, complete cds 3952 M00054645B:C12 MA187:B03 0.18868BC008092 gi|14198047|gb|BC008092.1BC008092 7.3E−105 Homo sapiens,ribosomal protein, large, P0, clone MGC: 9343 IMAGE: 3458803, mRNA,complete cds 3953 M00054646A:B10 MA187:C03 BC007097gi|13937968|gb|BC007097.1BC007097 5.2E−146 Homo sapiens, tissueinhibitor of metalloproteinase 1 (erythroid potentiating activity,collagena 3954 M00054647D:E01 MA187:G03 NM_001026gi|14916502|ref|NM_001026.2 Homo 6.4E−111 sapiens ribosomal protein S24(RPS24), transcript variant 2, mRNA 3955 M00057202C:G06 MA193:E03 3956M00057202D:C11 MA193:F03 X71973 gi|311699|emb|X71973.1HSGPX4 1.3E−26 H.sapiens GPx-4 mRNA for phospholipid hydroperoxide glutathione peroxidase3957 M00042549A:G12 MA167:C03 AF153609 gi|5231142|gb|AF153609.1AF1536091.8E−120 Homo sapiens serine/threonine protein kinase sgk mRNA, completecds 3958 M00042549D:F03 MA167:D03 BC011025gi|15029635|gb|BC011025.1BC011025 6.8E−34 Homo sapiens, Similar tosorcin, clone MGC: 13597 IMAGE: 4281626, mRNA, complete cds 3959M00042551B:D12 MA167:E03 NM_002295 gi|9845501|ref|NM_002295.2 Homo8.3E−226 sapiens laminin receptor 1 (67 kD, ribosomal protein SA)(LAMR1), mRNA 3960 M00042513A:D03 MA171:E03 NM_001002gi|16933547|ref|NM_001002.2 Homo 2.5E−266 sapiens ribosomal protein,large, P0 (RPLP0), transcript variant 1, mRNA 3961 M00042513D:A12MA171:F03 0.53205 3962 M00042551D:D12 MA167:H03 Z48514gi|695600|emb|Z48514.1HSXGR4551 2.8E−191 H. sapiens XG mRNA (cloneR4(551)) 3963 M00042717B:D05 MA167:A09 0.47619 X98311gi|1524059|emb|X98311.1HSCGM2ANT 1.1E−45 H. sapiens mRNA forcarcinoembryonic antigen family member 2, CGM2 3964 M00042719D:C09MA167:B09 L31792 gi|471076|gb|L31792.1HUMCGM2A 4.2E−144 Homo sapienscarcinoembryonic antigen (CGM2) mRNA, complete cds 3965 M00042803C:F11MA171:C09 M31520 gi|337504|gb|M31520.1HUMRPS24A 7.6E−120 Human ribosomalprotein S24 mRNA 3966 M00042805D:D12 MA171:E09 BC004324gi|13279235|gb|BC004324.1BC004324 2.4E−263 Homo sapiens, ribosomalprotein S16, clone MGC: 10931 IMAGE: 3628799, mRNA, complete cds 3967M00042731A:G04 MA167:F09 Z84867 gi|1834578|emb|Z84867.1HSZ84867 5.8E−113H. sapiens Ig lambda light chain variable region gene (14-09DPIA215)rearranged; Ig-Light-Lambda; VL 3968 M00042806C:E09 MA171:G09 0.12055U16738 gi|608516|gb|U16738.1HSU16738 Homo 1.4E−165 sapiens CAG-isl 7mRNA, complete cds 3969 M00042806D:F08 MA171:H09 Y16241gi|3378195|emb|Y16241.1HSY16241   3E−247 Homo sapiens mRNA for nebulette3970 M00056537A:F05 MA174:C03 NM_021130 gi|10863926|ref|NM_021130.1 Homo5.1E−249 sapiens peptidylprolyl isomerase A (cyclophilin A) (PPIA), mRNA3971 M00056537D:A07 MA174:D03 BC019255 gi|17939424|gb|BC019255.1BC0192552.3E−260 Homo sapiens, multifunctional polypeptide similar to SAICARsynthetase and AIR carboxylase, clone 3972 RG:1862584:20001:G03MA139:G03 0.72829 3973 M00056585D:D05 MA174:A09 BC007989gi|14124931|gb|BC007989.1BC007989 1.3E−283 Homo sapiens, Similar to heatshock 90 kD protein 1, alpha, clone IMAGE: 3030617, mRNA, partial cds3974 M00056586C:B08 MA174:B09 BC013873 gi|15530196|gb|BC013873.1BC0138731.2E−184 Homo sapiens, Similar to centrin, EF-hand protein, 2, cloneMGC: 10365 IMAGE: 3836808, mRNA, comple 3975 M00056592A:B08 MA174:E09AB018580 gi|6624210|dbj|AB018580.1AB018580 7.8E−251 Homo sapiens mRNAfor hluPGFS, complete cds 3976 RG:378550:10009:C03 MA158:C03 3977RG:789040:10011:F09 MA160:F09 M14676 gi|338227|gb|M14676.1HUMSLK Human  1E−300 src-like kinase (slk) mRNA, complete cds 3978 M00057283A:D01MA182:B03 AF283772 gi|10281741|gb|AF283772.2AF283772 2.5E−266 Homosapiens clone TCBAP0781 mRNA sequence 3979 M00043505A:E07 MA184:D03NM_007209 gi|16117792|ref|NM_007209.2 Homo 5.5E−258 sapiens ribosomalprotein L35 (RPL35), mRNA 3980 M00043506B:G10 MA184:G03 BC007945gi|14044036|gb|BC007945.1BC007945   1E−197 Homo sapiens, ribosomalprotein S11, clone MGC: 14322 IMAGE: 4297932, mRNA, complete cds 3981M00043507A:B02 MA184:H03 3982 M00042353C:F02 MA182:A09 NM_001015gi|14277698|ref|NM_001015.2 Homo 3.4E−256 sapiens ribosomal protein S11(RPS11), mRNA 3983 M00054516B:A08 MA184:F09 BC004459gi|13325289|gb|BC004459.1BC004459   5E−280 Homo sapiens, eukaryotictranslation initiation factor 4E binding protein 1, clone MGC: 4316IMAGE 3984 M00054986D:B04 MA198:A09 AJ131712gi|7576251|emb|AJ131712.1HSA131712 1.2E−168 Homo sapiens mRNA fornucleolar RNA- helicase (noH61 gene) 3985 M00054987C:B10 MA198:B090.09792 AF097362 gi|6165617|gb|AF097362.1AF097362 9.1E−139 Homo sapiensgamma-interferon inducible lysosomal thiol reductase (GILT) mRNA,complete cds 3986 M00054988D:B11 MA198:C09 BC019051gi|17403061|gb|BC019051.1BC019051 1.8E−192 Homo sapiens, clone IMAGE:4636237, mRNA 3987 M00055743C:G08 MA170:E03 BC018970gi|17512000|gb|BC018970.1BC018970 2.8E−216 Homo sapiens, ribosomalprotein L11, clone MGC: 19586 IMAGE: 4337066, mRNA, complete cds 3988M00055196B:C09 MA196:D03 BC018755 gi|17511806|gb|BC018755.1BC0187556.7E−242 Homo sapiens, PDZ and LIM domain 1 (elfin), clone MGC: 31954IMAGE: 3610938, mRNA, complete cds 3989 M00055238B:G05 MA196:B09NM_012423 gi|14591905|ref|NM_012423.2 Homo 3.8E−206 sapiens ribosomalprotein L13a (RPL13A), mRNA 3990 M00056207B:H06 MA180:G09 0.89703 3991M00055966C:G04 MA179:A03 BC008492 gi|14250147|gb|BC008492.1BC0084928.2E−282 Homo sapiens, ribosomal protein L3, clone MGC: 14821 IMAGE:4251511, mRNA, complete cds 3992 M00056920D:C08 MA177:A03 BC014301gi|15679985|gb|BC014301.1BC014301 8.8E−204 Homo sapiens, Similar toenhancer of rudimentary (Drosophila) homolog, clone MGC: 1509 IMAGE:35072 3993 M00055969D:D01 MA179:C03 0.16904 X73501gi|402644|emb|X73501.1HSCYTOK20   4E−225 H. sapiens gene for cytokeratin20 3994 M00056055D:F06 MA179:E09 AY011168 gi|12699140|gb|AY011168.1 Homo5.4E−149 sapiens 16S ribosomal RNA gene, partial sequence; mitochondrialgene for mitochondrial product 3995 M00056956B:G12 MA177:E09 0.870133996 M00056060D:C04 MA179:F09 V00710 gi|13683|emb|V00710.1MIT1HS Human  4E−184 mitochondrial genes for several tRNAs (Phe, Val, Leu) and 12Sand 16S ribosomal RNAs 3997 M00056061C:H04 MA179:G09 U14528gi|549987|gb|U14528.1HSU14528 Human 3.4E−219 sulfate transporter (DTD)mRNA, complete cds 3998 M00054743C:E05 MA188:A03 BC001603gi|12804402|gb|BC001603.1BC001603 2.3E−179 Homo sapiens, Similar toribosomal protein L21, clone MGC: 2150 IMAGE: 3543702, mRNA, completecds 3999 M00054744C:B02 MA188:B03 NM_033643 gi|16117795|ref|NM_033643.1Homo 6.2E−92 sapiens ribosomal protein L36 (RPL36), transcript variant1, mRNA 4000 M00054808A:E02 MA188:C09 BC003030gi|12804340|gb|BC003030.1BC003030 5.5E−174 Homo sapiens, heat shock 60kD protein 1 (chaperonin), clone MGC: 4335 IMAGE: 2821157, mRNA, complet4001 M00054811A:G01 MA188:G09 X90583 gi|1071680|emb|X90583.1HSRNATRAP3.9E−184 H. sapiens mRNA for rat translocon- associated protein deltahomolog 4002 M00054797C:G10 MA168:A03 BC004983gi|13436415|gb|BC004983.1BC004983 2.1E−148 Homo sapiens, nuclear factorof kappa light polypeptide gene enhancer in B-cells inhibitor, alpha4003 M00042843B:H01 MA172:A03 AF068754 gi|3283408|gb|AF068754.1AF0687547.8E−139 Homo sapiens heat shock factor binding protein 1 HSBP1 mRNA,complete cds 4004 M00042844D:D10 MA172:D03 BC000483gi|12653424|gb|BC000483.1BC000483 2.3E−232 Homo sapiens, clone MGC: 8704IMAGE: 2964733, mRNA, complete cds 4005 M00042845D:A12 MA172:E03BC008329 gi|14249899|gb|BC008329.1BC008329 8.5E−229 Homo sapiens, cloneMGC: 15787 IMAGE: 3504130, mRNA, complete cds 4006 M00054800C:H10MA168:G03 Z85052 gi|1834763|emb|Z85052.1HSZ85052   9E−167 H. sapiens Iglambda light chain variable region gene (26-34ITIIIF120) rearranged;Ig-Light-Lambda; 4007 M00054911D:E09 MA168:H03 NM_000969gi|14591908|ref|NM_000969.2 Homo 7.2E−217 sapiens ribosomal protein L5(RPL5), mRNA 4008 M00055450A:G03 MA168:A09 0.09821 AF074331gi|5052074|gb|AF074331.1AF074331 6.8E−152 Homo sapiens PAPS synthetase-2(PAPSS2) mRNA, complete cds 4009 M00055456B:H05 MA168:D09 0.79701 4010M00056733C:D03 MA175:D03 X97336 gi|1666193|emb|X97336.1RUMTGENOM 3.1E−72Rhinoceros unicornis complete mitochondrial genome 4011 M00056737D:E08MA175:H03 D11094 gi|219930|dbj|D11094.1HUMMSS1 5.9E−230 Human mRNA forMSS1, complete cds 4012 M00056809B:A12 MA175:E09 L42345gi|1160933|gb|L42345.1HUMHLAB44A   6E−152 Homo sapiens lymphocyteantigen HLA- B*4402 and HLA-B*5101 mRNA, exons 1-7, complete cds 4013M00056809D:C07 MA175:G09 J03801 gi|187243|gb|J03801.1HUMLSZ Human9.3E−207 lysozyme mRNA, complete cds with an Alu repeat in the 3′ flank4014 RG:1664308:10014:F09 MA163:F09 AF011497gi|2286216|gb|AF011497.1AF011497 0 Homo sapiens guanine nucleotidebinding protein alpha 11 subunit (G11) mRNA, complete cds 4015M00043321A:G07 MA183:B03 D49400 gi|1395161|dbj|D49400.1HUMVATPASE5.1E−280 Homo sapiens mRNA for vacuolar ATPase, complete cds 4016M00054549A:F03 MA185:C03 0.84052 4017 M00043381A:C08 MA183:D09 NM_001012gi|4506742|ref|NM_001012.1 Homo 1.1E−231 sapiens ribosomal protein S8(RPS8), mRNA 4018 M00056642B:G03 MA186:A03 BC010952gi|15012094|gb|BC010952.1BC010952   1E−300 Homo sapiens, Similar toprotease inhibitor 3, skin-derived (SKALP), clone MGC: 13613 IMAGE:408315 4019 M00056688C:A07 MA186:H09 D13748 gi|219402|dbj|D13748.1HUM4AIHuman   1E−300 mRNA for eukaryotic initiation factor 4AI 4020M00056257C:G03 MA181:A04 AK054673 gi|16549265|dbj|AK054673.1AK0546733.6E−228 Homo sapiens cDNA FLJ30111 fis, clone BNGH42000360, highlysimilar to 3- KETOACYL-COA THIOLASE MI 4021 M00055545C:F11 MA169:G04AY029066 gi|14017398|gb|AY029066.1 Homo 1.4E−258 sapiens Humanin (HN1)mRNA, complete cds 4022 M00055653C:F04 MA169:C10 M10050gi|182355|gb|M10050.1HUMFABPL   5E−224 Human liver fatty acid bindingprotein (FABP) mRNA, complete cds 4023 M00055653D:F01 MA169:D10 M10050gi|182355|gb|M10050.1HUMFABPL 1.9E−167 Human liver fatty acid bindingprotein (FABP) mRNA, complete cds 4024 M00055385A:C11 MA197:B10 BC013231gi|15301504|gb|BC013231.1BC013231 2.9E−244 Homo sapiens, clone IMAGE:3462987, mRNA 4025 M00056157A:F11 MA180:D04 X74104gi|452756|emb|X74104.1HSSSR H. sapiens 4.5E−274 mRNA for TRAP betasubunit 4026 M00056160A:F03 MA180:E04 0.89209 4027 M00056426A:H07MA173:F04 0.49541 4028 M00056214C:B04 MA180:C10 Y00339gi|29586|emb|Y00339.1HSCA2 Human   3E−222 mRNA for carbonic anhydrase II(EC 4.2.1.1) 4029 M00056216A:F10 MA180:D10 0.75335 4030 M00056507A:G11MA173:G10 0.71615 4031 M00054648C:C10 MA187:A04 BC004113gi|13278665|gb|BC004113.1BC004113 1.6E−236 Homo sapiens, Similar tonon-POU- domain-containing, octamer-binding, clone IMAGE: 3835400, mRNA,p 4032 M00054862A:H11 MA189:A04 0.60181 4033 M00054648D:F12 MA187:B04BC001118 gi|12654566|gb|BC001118.1BC001118 1.5E−289 Homo sapiens,Similar to seven transmembrane domain protein, clone MGC: 1936 IMAGE:2989840, mRNA, 4034 M00054650C:H08 MA187:D04 AB026723gi|5931601|dbj|AB026723.1AB026723 1.6E−295 Homo sapiens SID6-8061 mRNAfor pyrophosphatase, complete cds 4035 M00054868C:C11 MA189:H04 0.097034036 M00054700C:E02 MA187:D10 BC000530 gi|12653516|gb|BC000530.1BC0005302.9E−244 Homo sapiens, ribosomal protein L19, clone MGC: 8653 IMAGE:2961653, mRNA, complete cds 4037 M00054902D:G11 MA189:F10 0.71088 4038M00054903B:G06 MA189:G10 BC013231 gi|15301504|gb|BC013231.1BC0132311.1E−240 Homo sapiens, clone IMAGE: 3462987, mRNA 4039 M00054706A:D05MA187:H10 AB060236 gi|13676490|dbj|AB060236.1AB060236 6.9E−71 Macacafascicularis brain cDNA clone: QflA-11918, full insert sequence 4040M00057207A:D05 MA193:C04 AF127763 gi|6138993|gb|AF127763.2AF1277632.7E−297 Homo sapiens mitogenic oxidase mRNA, complete cds 4041M00057207C:F06 MA193:D04 BC016756 gi|16876963|gb|BC016756.1BC0167569.4E−291 Homo sapiens, glutathione peroxidase 2 (gastrointestinal),clone IMAGE: 3681457, mRNA 4042 M00057208B:F11 MA193:F04 X60489gi|31099|emb|X60489.1HSEF1B Human   8E−279 mRNA for elongationfactor-1-beta 4043 M00057242B:B10 MA193:C10 J03464gi|179595|gb|J03464.1HUMC1A2 Human 2.1E−282 collagen alpha-2 type ImRNA, complete cds, clone pHCOL2A1 4044 M00042555A:E06 MA167:C04 0.792494045 M00042561A:H03 MA167:D04 AK057546gi|16553292|dbj|AK057546.1AK057546 3.1E−278 Homo sapiens cDNA FLJ32984fis, clone THYMU1000017, highly similar to Homo sapiens splice varian4046 M00042756C:E10 MA171:E04 NM_005348 gi|13129149|ref|NM_005348.1 Homo  3E−222 sapiens heat shock 90 kD protein 1, alpha (HSPCA), mRNA 4047M00042758D:F01 MA171:F04 NM_000969 gi|14591908|ref|NM_000969.2 Homo3.7E−259 sapiens ribosomal protein L5 (RPL5), mRNA 4048 M00042759B:E02MA171:H04 BC000077 gi|12652658|gb|BC000077.1BC000077 5.1E−252 Homosapiens, ribosomal protein L8, clone MGC: 3253 IMAGE: 3506015, mRNA,complete cds 4049 M00042808D:D03 MA171:B10 AB048207gi|15425668|dbj|AB048207.1AB048207 2.2E−257 Homo sapiens mRNA for TIGA1,complete cds 4050 M00042808D:D10 MA171:C10 AK026166gi|10438929|dbj|AK026166.1AK026166 9.5E−263 Homo sapiens cDNA: FLJ22513fis, clone HRC12111, highly similar to HUMKUP Human Ku (p70/p80) sub4051 M00042811B:A05 MA171:D10 AK027191gi|10440260|dbj|AK027191.1AK027191 1.6E−121 Homo sapiens cDNA: FLJ23538fis, clone LNG08010, highly similar to BETA2 Human MEN1 region clone4052 M00042746B:F05 MA167:E10 AK026528gi|10439405|dbj|AK026528.1AK026528 1.6E−77 Homo sapiens cDNA: FLJ22875fis, clone KAT02879 4053 M00042746C:D01 MA167:G10 BC000551gi|12653554|gb|BC000551.1BC000551   5E−128 Homo sapiens,lysophospholipase-like, clone MGC: 1216 IMAGE: 3163689, mRNA, completecds 4054 M00042812D:B04 MA171:G10 NM_000978 gi|14591907|ref|NM_000978.2Homo 3.5E−256 sapiens ribosomal protein L23 (RPL23), mRNA 4055M00056546B:F12 MA174:A04 AK026570 gi|10439452|dbj|AK026570.1AK0265702.1E−226 Homo sapiens cDNA: FLJ22917 fis, clone KAT06430 4056M00056550A:G09 MA174:H04 X14420 gi|30057|emb|X14420.1HSCOL3AI 5.1E−165Human mRNA for pro-alpha-1 type 3 collagen 4057 M00056610C:B08 MA174:G10D87667 gi|1620019|dbj|D87667.1D87667 Human 1.4E−199 brain mRNAhomologous to 3′UTR of human CD24 gene, partial sequence 4058RG:745556:10011:B04 MA160:B04 AK056676gi|16552146|dbj|AK056676.1AK056676 8.7E−227 Homo sapiens cDNA FLJ32114fis, clone OCBBF2001706 4059 RG:446537:10009:G04 MA158:G04 BC001430gi|12655150|gb|BC001430.1BC001430 0 Homo sapiens, POP7 (processing ofprecursor, S. cerevisiae) homolog, clone MGC: 1986 IMAGE: 3138336 4060RG:375937:10009:B10 MA158:B10 BC010153 gi|14603405|gb|BC010153.1BC0101531.1E−77 Homo sapiens, cyclin-dependent kinase 4, clone MGC: 19704 IMAGE:3531300, mRNA, complete cds 4061 RG:755120:10011:B10 MA160:B10 BC016725gi|16876888|gb|BC016725.1BC016725 3.5E−52 Homo sapiens, 60S ribosomalprotein L30 isolog, clone MGC: 24451 IMAGE: 4078305, mRNA, complete cds4062 RG:781108:10011:D10 MA160:D10 4063 M00042450C:H10 MA182:A10 S56985gi|298485|gb|S56985.1S56985 ribosomal 1.4E−258 protein L19 [human,breast cancer cell line, MCF-7, mRNA, 690 nt] 4064 M00042451B:B05MA182:B10 BC013231 gi|15301504|gb|BC013231.1BC013231 1.7E−239 Homosapiens, clone IMAGE: 3462987, mRNA 4065 M00054517D:D12 MA184:B10NM_000661 gi|15431302|ref|NM_000661.2 Homo   1E−156 sapiens ribosomalprotein L9 (RPL9), mRNA 4066 M00055002B:G06 MA198:D10 J04164gi|177801|gb|J04164.1HUM927A Human 1.5E−177 interferon-inducible protein9-27 mRNA, complete cds 4067 M00055749A:C09 MA170:B04 0.08723 M36532gi|179794|gb|M36532.1HUMCAIZ Human 1.8E−236 carbonic anhydrase II mRNA,complete cds 4068 M00055750A:F10 MA170:D04 X57809gi|33714|emb|X57809.1HSIGVL009 4.1E−178 Human rearranged immunoglobulinlambda light chain mRNA 4069 M00055757A:H06 MA170:G04 M12759gi|532596|gb|M12759.1HUMIGJ02 2.6E−104 Human Ig J chain gene, exons 3and 4 4070 M00055200B:F03 MA196:D04 AK056446gi|16551850|dbj|AK056446.1AK056446 2.3E−232 Homo sapiens cDNA FLJ31884fis, clone NT2RP7002906, highly similar to HEAT SHOCK PROTEIN HSP 90-4071 M00055203B:F05 MA196:F04 NM_000979 gi|15431298|ref|NM_000979.2 Homo3.8E−262 sapiens ribosomal protein L18 (RPL18), mRNA 4072 M00055980B:F12MA179:E04 AK000140 gi|7020034|dbj|AK000140.1AK000140 6.8E−270 Homosapiens cDNA FLJ20133 fis, clone COL06539 4073 M00056066C:H10 MA179:B100.89137 4074 M00056067B:F12 MA179:C10 BC011836gi|15080121|gb|BC011836.1BC011836 7.1E−273 Homo sapiens, clone IMAGE:3945177, mRNA 4075 M00056075D:H10 MA179:D10 AK027140gi|10440192|dbj|AK027140.1AK027140 3.3E−200 Homo sapiens cDNA: FLJ23487fis, clone LNG00423 4076 M00056962D:A05 MA177:D10 BC017366gi|16924194|gb|BC017366.1BC017366 2.4E−91 Homo sapiens, clone MGC: 1191IMAGE: 3506054, mRNA, complete cds 4077 M00056081D:B09 MA179:E10AF346964 gi|13272570|gb|AF346964.1AF346964 1.9E−93 Homo sapiensmitochondrion, complete genome 4078 M00056963A:E01 MA177:E10 BC000999gi|12803040|gb|BC000999.2BC000999 1.9E−276 Homo sapiens, Similar totransforming, acidic coiled-coil containing protein 2, clone IMAGE:29849 4079 M00056081D:C02 MA179:F10 V00710 gi|13683|emb|V00710.1MIT1HSHuman 1.3E−97 mitochondrial genes for several tRNAs (Phe, Val, Leu) and12S and 16S ribosomal RNAs 4080 M00056964D:C08 MA177:G10 M36072gi|337494|gb|M36072.1HUMRPL7A 1.8E−245 Human ribosomal protein L7a (surf3) large subunit mRNA, complete cds 4081 M00056084A:B08 MA179:H10 U67963gi|1763010|gb|U67963.1HSU67963 2.3E−136 Human lysophospholipase homolog(HU- K5) mRNA, complete cds 4082 M00054750C:G08 MA188:B04 BC001125gi|12654578|gb|BC001125.1BC001125 1.1E−190 Homo sapiens, peptidylprolylisomerase B (cyclophilin B), clone MGC: 2224 IMAGE: 2966791, mRNA, com4083 M00054750D:F04 MA188:C04 U30246 gi|903681|gb|U30246.1HSU30246 Human  3E−247 bumetanide-sensitive Na—K—Cl cotransporter (NKCC1) mRNA,complete cds 4084 M00054757A:F05 MA188:G04 U86602gi|1835785|gb|U86602.1HSU86602   1E−300 Human nucleolar protein p40mRNA, complete cds 4085 M00054760D:B10 MA188:H04 BC014788gi|15928638|gb|BC014788.1BC014788   1E−300 Homo sapiens, guaninenucleotide binding protein (G protein), beta polypeptide 2-like 1, cloneMG 4086 M00042847A:A04 MA172:A04 M61831 gi|178276|gb|M61831.1HUMAHCY5.5E−230 Human S-adenosylhomocysteine hydrolase (AHCY) mRNA, completecds 4087 M00042847A:D10 MA172:B04 0.82393 4088 M00054917B:G02 MA168:F04J04164 gi|177801|gb|J04164.1HUM927A Human 6.4E−239 interferon-inducibleprotein 9-27 mRNA, complete cds 4089 M00055468D:D05 MA168:C10 BC001781gi|12804704|gb|BC001781.1BC001781 2.2E−173 Homo sapiens, ribosomalprotein L44, clone MGC: 2064 IMAGE: 3353669, mRNA, complete cds 4090M00055469B:E11 MA168:D10 0.52048 U07969 gi|483391|gb|U07969.1HSU07969Human 7.2E−103 intestinal peptide-associated transporter HPT-1 mRNA,complete cds 4091 M00055492C:C01 MA168:G10 BC003394gi|13097278|gb|BC003394.1BC003394 3.2E−253 Homo sapiens, heterogeneousnuclear ribonucleoprotein C (C1/C2), clone MGC: 5418 IMAGE: 3447724, mR4092 M00055496A:E06 MA168:H10 0.86834 4093 M00056742D:D01 MA175:F04U51924 gi|1263307|gb|U51924.1HSU51924 1.3E−199 Human phosphatase 2Ainhibitor I2PP2A mRNA, complete cds 4094 M00056814D:C08 MA175:G10BC000472 gi|12653404|gb|BC000472.1BC000472 2.4E−291 Homo sapiens,ribosomal protein S4, X- linked, clone MGC: 8636 IMAGE: 2961540, mRNA,complete cds 4095 RG:1636303:10014:B10 MA163:B10 AJ338808gi|15883226|emb|AJ338808.1HSA338808 0 Homo sapiens genomic sequencesurrounding NotI site, clone NR1-QA13R 4096 RG:1643142:10014:C10MA163:C10 U14528 gi|549987|gb|U14528.1HSU14528 Human 5.6E−138 sulfatetransporter (DTD) mRNA, complete cds 4097 RG:1650444:10014:D10 MA163:D10D10040 gi|219899|dbj|D10040.1HUMLCACS 0 Homo sapiens mRNA for long-chainacyl- CoA synthetase, complete cds 4098 RG:1418984:10003:H10 MA152:H10X52967 gi|36139|emb|X52967.1HSRPL7 Human   1E−300 mRNA for ribosomalprotein L7 4099 M00043339C:C12 MA183:A04 X60489gi|31099|emb|X60489.1HSEF1B Human   7E−270 mRNA for elongationfactor-1-beta 4100 M00043342C:H03 MA183:B04 AK026558gi|10439440|dbj|AK026558.1AK026558 4.1E−159 Homo sapiens cDNA: FLJ22905fis, clone KAT05654, highly similar to HUMRPL18A Homo sapiens riboso4101 M00043350A:C04 MA183:D04 BC004324 gi|13279235|gb|BC004324.1BC0043243.7E−231 Homo sapiens, ribosomal protein S16, clone MGC: 10931 IMAGE:3628799, mRNA, complete cds 4102 M00056646D:G05 MA186:B04 BC018190gi|17390422|gb|BC018190.1BC018190 3.4E−172 Homo sapiens, Similar tometallothionein 1L, clone MGC: 9187 IMAGE: 3859643, mRNA, complete cds4103 M00055406C:H08 MA199:D04 AF078861 gi|5531836|gb|AF078861.1AF0788611.8E−192 Homo sapiens PTD008 mRNA, complete cds 4104 M00056653C:F06MA186:H04 BC005354 gi|13529169|gb|BC005354.1BC005354 1.6E−264 Homosapiens, ribosomal protein, large P2, clone MGC: 12453 IMAGE: 4052568,mRNA, complete cds 4105 M00055408A:H06 MA199:H04 AF054183gi|4092053|gb|AF054183.1AF054183   1E−187 Homo sapiens GTP bindingprotein mRNA, complete cds 4106 M00055545D:E02 MA169:A05 BC009699gi|16307220|gb|BC009699.1BC009699   5E−224 Homo sapiens, Similar to RNAhelicase- related protein, clone MGC: 9246 IMAGE: 3892441, mRNA, comple4107 M00055548B:H07 MA169:C05 AF105253 gi|7532779|gb|AF105253.1AF1052534.2E−268 Homo sapiens neuroendocrine secretory protein 55 mRNA, completecds 4108 M00056271C:F02 MA181:D05 BC008323gi|14249887|gb|BC008323.1BC008323 5.8E−202 Homo sapiens, clone MGC:15764 IMAGE: 3358085, mRNA, complete cds 4109 M00055550D:A05 MA169:F05AF130094 gi|11493492|gb|AF130094.1AF130094 3.4E−225 Homo sapiens cloneFLC0165 mRNA sequence 4110 M00055661A:F09 MA169:E11 4111 M00056427D:A09MA173:B05 U07550 gi|469170|gb|U07550.1HSU07550 Human   2E−145 chaperonin10 mRNA, complete cds 4112 M00056163C:H09 MA180:B05 AF201944gi|9295191|gb|AF201944.1AF201944 2.2E−285 Homo sapiens HGTD-P (HGTD-P)mRNA, complete cds 4113 M00056428B:F07 MA173:C05 U30246gi|903681|gb|U30246.1HSU30246 Human 9.7E−126 bumetanide-sensitiveNa—K—Cl cotransporter (NKCC1) mRNA, complete cds 4114 M00056163D:E01MA180:C05 BC001829 gi|12804776|gb|BC001829.1BC001829 4.4E−240 Homosapiens, lactate dehydrogenase A, clone MGC: 4065 IMAGE: 2960999, mRNA,complete cds 4115 M00056428C:A12 MA173:E05 NM_001016gi|14277699|ref|NM_001016.2 Homo 4.2E−212 sapiens ribosomal protein S12(RPS12), mRNA 4116 M00056429D:D07 MA173:F05 0.53763 4117 M00056175D:B05MA180:G05 Z62862 gi|1035240|emb|Z62862.1HS74B1R 6.9E−87 H. sapiens CpGisland DNA genomic Mse1 fragment, clone 74b1, reverse read cpg74b1.rt1a4118 M00056507D:D04 MA173:A11 0.65197 4119 M00056511D:H07 MA173:F11BC000419 gi|12653300|gb|BC000419.1BC000419 6.1E−205 Homo sapiens,catechol-O- methyltransferase, clone MGC: 8663 IMAGE: 2964400, mRNA,complete cds 4120 M00054654A:F12 MA187:A05 NM_000976gi|15431291|ref|NM_000976.2 Homo   1E−296 sapiens ribosomal protein L12(RPL12), mRNA 4121 M00054868D:F12 MA189:A05 NM_012423gi|14591905|ref|NM_012423.2 Homo 4.4E−140 sapiens ribosomal protein L13a(RPL13A), mRNA 4122 M00054661B:H10 MA187:D05 L47277gi|986911|gb|L47277.1HUMTOPATRA 5.8E−261 Homo sapiens (cell line HepG2,HeLa) alpha topoisomerase truncated-form mRNA, 3′UTR 4123 M00054666B:C07MA187:F05 AJ250229 gi|8926686|emb|AJ250229.1HSA250229 6.1E−205 Homosapiens mRNA for chromosome 11 hypothetical protein (ORF1) 4124M00054870B:H05 MA189:F05 M26326 gi|186690|gb|M26326.1HUMKER18AA 4.8E−121Human keratin 18 mRNA, complete cds 4125 M00054669B:B03 MA187:G05BC001754 gi|12804658|gb|BC001754.1BC001754   8E−192 Homo sapiens,male-enhanced antigen, clone MGC: 2286 IMAGE: 3355279, mRNA, completecds 4126 M00054706B:G04 MA187:A11 AF201944gi|9295191|gb|AF201944.1AF201944 8.3E−251 Homo sapiens HGTD-P (HGTD-P)mRNA, complete cds 4127 M00054720C:F01 MA187:D11 BC013918gi|15530264|gb|BC013918.1BC013918 1.4E−224 Homo sapiens, Similar toeukaryotic translation elongation factor 1 gamma, clone MGC: 22883IMAGE: 4128 M00054722B:E08 MA187:E11 Z62862gi|1035240|emb|Z62862.1HS74B1R   6E−116 H. sapiens CpG island DNAgenomic Mse1 fragment, clone 74b1, reverse read cpg74b1.rt1a 4129M00054908A:H08 MA189:E11 L00160 gi|189904|gb|L00160.1HUMPGK2 Human2.4E−291 phosphoglycerate kinase (pgk) mRNA, exons 2 to last 4130M00054723B:H12 MA187:G11 X60819 gi|34458|emb|X60819.1HSMAOP14 1.6E−295H. sapiens DNA for monoamine oxidase type A (14) (partial) 4131M00057210B:G10 MA193:C05 U12404 gi|531170|gb|U12404.1HSU12404 Human3.5E−175 Csa-19 mRNA, complete cds 4132 M00057248D:B05 MA193:B11NM_001024 gi|14670385|ref|NM_001024.2 Homo 1.3E−196 sapiens ribosomalprotein S21 (RPS21), mRNA 4133 M00057252A:F06 MA193:F11 AF035555gi|3116433|gb|AF035555.1AF035555 2.5E−182 Homo sapiens short chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) mRNA, complete cds 4134M00042573B:A02 MA167:B05 BC007583 gi|14043190|gb|BC007583.1BC0075831.6E−102 Homo sapiens, clone MGC: 15572 IMAGE: 3140342, mRNA, completecds 4135 M00042766A:E10 MA171:F05 AF201944gi|9295191|gb|AF201944.1AF201944 2.8E−244 Homo sapiens HGTD-P (HGTD-P)mRNA, complete cds 4136 M00042882D:G08 MA167:A11 AF346964gi|13272570|gb|AF346964.1AF346964 5.1E−199 Homo sapiens mitochondrion,complete genome 4137 M00042885C:A12 MA167:B11 NM_001018gi|14591911|ref|NM_001018.2 Homo 1.9E−248 sapiens ribosomal protein S15(RPS15), mRNA 4138 M00042815A:E07 MA171:B11 0.781 4139 M00042817B:E11MA171:C11 AF077034 gi|4689115|gb|AF077034.1AF077034 5.6E−258 Homosapiens HSPC010 mRNA, complete cds 4140 M00042887C:A07 MA167:E11 X73502gi|406853|emb|X73502.1HSENCY20 H. sapiens 2.1E−195 mRNA for cytokeratin20 4141 M00042818D:A08 MA171:G11 NM_001002 gi|16933547|ref|NM_001002.2Homo   2E−251 sapiens ribosomal protein, large, P0 (RPLP0), transcriptvariant 1, mRNA 4142 M00056552A:G08 MA174:C05 AK027892gi|14042896|dbj|AK027892.1AK027892 2.4E−291 Homo sapiens cDNA FLJ14986fis, clone Y79AA1000784, highly similar to Homo sapiens RanBP7/import4143 M00056552C:D08 MA174:D05 BC017831 gi|17389602|gb|BC017831.1BC017831  2E−279 Homo sapiens, ribosomal protein L17, clone MGC: 22482 IMAGE:4251433, mRNA, complete cds 4144 M00056553C:E10 MA174:E05 X14420gi|30057|emb|X14420.1HSCOL3AI 5.8E−289 Human mRNA for pro-alpha-1 type 3collagen 4145 M00056555B:C11 MA174:H05 M58458gi|337509|gb|M58458.1HUMRPS4X 1.2E−196 Human ribosomal protein S4(RPS4X) isoform mRNA, complete cds 4146 M00056611C:D03 MA174:D11AF081192 gi|3420798|gb|AF081192.1AF081192 3.9E−293 Homo sapiens histoneH2A.F/Z variant (H2AV) mRNA, complete cds 4147 M00056611D:B03 MA174:F11L06498 gi|292442|gb|L06498.1HUMRPS20 Homo   3E−169 sapiens ribosomalprotein S20 (RPS20) mRNA, complete cds 4148 M00056611D:F08 MA174:G11M19645 gi|183644|gb|M19645.1HUMGRP78 1.5E−289 Human 78 kdaltonglucose-regulated protein (GRP78) gene, complete cds 4149 M00056614C:F06MA174:H11 AB063318 gi|14517631|dbj|AB063318.1AB063318 5.7E−230 Homosapiens MoDP-2, MoDP-3 mRNA for acute morphine dependence relatedprotein 2, acute morphine 4150 RG:358387:10009:A05 MA158:A05 BC014270gi|15679933|gb|BC014270.1BC014270 2.9E−266 Homo sapiens, protein kinaseC, zeta, clone MGC: 10512 IMAGE: 3835020, mRNA, complete cds 4151M00057302A:F08 MA182:A05 BC007097 gi|13937968|gb|BC007097.1BC0070973.3E−147 Homo sapiens, tissue inhibitor of metalloproteinase 1(erythroid potentiating activity, collagena 4152 M00057302C:H09MA182:C05 BC018210 gi|17390469|gb|BC018210.1BC018210 2.1E−251 Homosapiens, tubulin-specific chaperone a, clone MGC: 9129 IMAGE: 3861138,mRNA, complete cds 4153 M00054496A:B09 MA184:F05 0.60245 BC002589gi|12803524|gb|BC002589.1BC002589 3.5E−64 Homo sapiens, proteasome(prosome, macropain) 26S subunit, ATPase, 2, clone MGC: 3004 IMAGE:316179 4154 M00054496A:H05 MA184:H05 BC004138gi|13278716|gb|BC004138.1BC004138 1.4E−286 Homo sapiens, ribosomalprotein L6, clone MGC: 1635 IMAGE: 2823733, mRNA, complete cds 4155M00042460B:A08 MA182:A11 NM_000980 gi|15431299|ref|NM_000980.2 Homo8.7E−229 sapiens ribosomal protein L18a (RPL18A), mRNA 4156M00054524B:B09 MA184:A11 NM_000976 gi|15431291|ref|NM_000976.2 Homo4.1E−296 sapiens ribosomal protein L12 (RPL12), mRNA 4157 M00054526C:E05MA184:B11 NM_000988 gi|17017972|ref|NM_000988.2 Homo   7E−189 sapiensribosomal protein L27 (RPL27), mRNA 4158 M00042516B:A08 MA182:C11NM_000976 gi|15431291|ref|NM_000976.2 Homo   2E−248 sapiens ribosomalprotein L12 (RPL12), mRNA 4159 M00042517D:H10 MA182:D11 BC000386gi|12653234|gb|BC000386.1BC000386 3.8E−178 Homo sapiens, eukaryotictranslation initiation factor 3, subunit 3 (gamma, 40 kD), clone MGC:8431 4160 M00054527B:H11 MA184:D11 AF155235gi|6318598|gb|AF155235.1AF155235 4.5E−240 Homo sapiens 15.5 kD RNAbinding protein mRNA, complete cds 4161 M00042517D:H11 MA182:E11BC016756 gi|16876963|gb|BC016756.1BC016756 1.4E−230 Homo sapiens,glutathione peroxidase 2 (gastrointestinal), clone IMAGE: 3681457, mRNA4162 M00054529C:G04 MA184:G11 NM_022551 gi|14165467|ref|NM_022551.2 Homo2.7E−213 sapiens ribosomal protein S18 (RPS18), mRNA 4163 M00043300D:A06MA182:H11 BC012146 gi|15082460|gb|BC012146.1BC012146 3.6E−259 Homosapiens, Similar to ribosomal protein L3, clone MGC: 20359 IMAGE:4549682, mRNA, complete cds 4164 M00054958A:G10 MA198:C05 AY007723gi|15431041|gb|AY007723.1 Homo 2.6E−185 sapiens MAL2 proteolipid (MAL2)mRNA, complete cds 4165 M00054958B:B07 MA198:D05 0.12023 AF012108gi|2331249|gb|AF012108.1AF012108 2.6E−111 Homo sapiens Amplified inBreast Cancer (AIB1) mRNA, complete cds 4166 M00054961D:E08 MA198:H05NM_005617 gi|14141191|ref|NM_005617.2 Homo 3.2E−172 sapiens ribosomalprotein S14 (RPS14), mRNA 4167 M00055015C:H02 MA198:C11 X58965gi|35069|emb|X58965.1HSNM23H2G 4.4E−187 H. sapiens RNA for nm23-H2 gene4168 M00055016B:D03 MA198:E11 NM_001010 gi|17158043|ref|NM_001010.2 Homo1.7E−186 sapiens ribosomal protein S6 (RPS6), mRNA 4169 M00055764D:D05MA170:E05 BC001708 gi|12804576|gb|BC001708.1BC001708 9.8E−210 Homosapiens, ribosomal protein S3A, clone MGC: 1626 IMAGE: 3544072, mRNA,complete cds 4170 M00055815C:E08 MA170:B11 AK025459gi|10437979|dbj|AK025459.1AK025459 4.8E−249 Homo sapiens cDNA: FLJ21806fis, clone HEP00829, highly similar to HSTRA1 Human tra1 mRNA for hu4171 M00055819B:B12 MA170:F11 AF014838 gi|2281706|gb|AF014838.1AF0148388.3E−254 Homo sapiens galectin-4 mRNA, complete cds 4172 M00055820C:H11MA170:H11 NM_000967 gi|16507968|ref|NM_000967.2 Homo 3.4E−175 sapiensribosomal protein L3 (RPL3), mRNA 4173 M00055204B:C04 MA196:A05 X57351gi|311373|emb|X57351.1HS18D Human 1- 1.2E−218 8D gene frominterferon-inducible gene family 4174 M00055209A:C09 MA196:D05 AF028832gi|3287488|gb|AF028832.1AF028832 9.1E−232 Homo sapiensHsp89-alpha-delta-N mRNA, complete cds 4175 M00055252C:G12 MA196:D110.1038 U16738 gi|608516|gb|U16738.1HSU16738 Homo   1E−172 sapiensCAG-isl 7 mRNA, complete cds 4176 M00056934C:D08 MA177:A05 Z69043gi|2398656|emb|Z69043.1HSTRAPRNA 3.2E−281 H. sapiens mRNAtranslocon-associated protein delta subunit precursor 4177M00055989C:D03 MA179:B05 0.8 4178 M00056937C:G12 MA177:D05 AK055020gi|16549662|dbj|AK055020.1AK055020 3.2E−219 Homo sapiens cDNA FLJ30458fis, clone BRACE2009421, highly similar to NUCLEOSOME ASSEMBLY PROTEI4179 M00055997B:A02 MA179:H05 0.89264 4180 M00056087A:G01 MA179:C11AF150754 gi|12484558|gb|AF150754.2AF150754 2.4E−96 Homo sapiens3′phosphoadenosine 5′- phosphosulfate synthase 2b isoform mRNA, completecds 4181 M00056091A:H05 MA179:D11 BC013724gi|15489238|gb|BC013724.1BC013724 3.9E−265 Homo sapiens, ferritin, heavypolypeptide 1, clone MGC: 17255 IMAGE: 3857790, mRNA, complete cds 4182M00056966B:A05 MA177:E11 AF346974 gi|13272710|gb|AF346974.1AF3469745.6E−108 Homo sapiens mitochondrion, complete genome 4183 M00056093A:F08MA179:F11 0.26754 4184 M00056096C:H10 MA179:H11 0.77419 4185M00054766B:E10 MA188:H05 BC005328 gi|13529103|gb|BC005328.1BC0053285.8E−258 Homo sapiens, ribosomal protein S27a, clone MGC: 12414, mRNA,complete cds 4186 M00054817B:H09 MA188:B11 BC015465gi|15930040|gb|BC015465.1BC015465 8.4E−254 Homo sapiens, HSPC023protein, clone MGC: 8754 IMAGE: 3914049, mRNA, complete cds 4187M00054818D:G04 MA188:D11 BC008495 gi|14250151|gb|BC008495.1BC0084951.4E−258 Homo sapiens, nucleophosmin (nucleolar phosphoprotein B23,numatrin), clone MGC: 14826 IMAGE: 42766 4188 M00042851D:H04 MA172:A05NM_001000 gi|16306563|ref|NM_001000.2 Homo 3.7E−156 sapiens ribosomalprotein L39 (RPL39), mRNA 4189 M00042853A:F01 MA172:B05 NM_000970gi|16753226|ref|NM_000970.2 Homo 3.4E−284 sapiens ribosomal protein L6(RPL6), mRNA 4190 M00055426A:G06 MA168:E05 AF272149gi|9971873|gb|AF272149.1AF272149 1.3E−61 Homo sapiens hepatocellularcarcinoma associated-gene TB6, mRNA sequence 4191 M00055496A:G12MA168:B11 AF203815 gi|6979641|gb|AF203815.1AF203815 5.6E−202 Homosapiens alpha gene sequence 4192 M00055509C:C02 MA168:F11 0.76684AL590401 gi|14422235|emb|AL590401.6AL590401 1.8E−35 Human DNA sequencefrom clone RP11- 466P12 on chromosome 6, complete sequence [Homosapiens] 4193 M00055510B:F08 MA168:G11 AF067174gi|4894381|gb|AF067174.1AF067174 2.2E−257 Homo sapiens retinoldehydrogenase homolog mRNA, complete cds 4194 M00055510D:A08 MA168:H11AK026649 gi|10439547|dbj|AK026649.1AK026649 1.6E−161 Homo sapiens cDNA:FLJ22996 fis, clone KAT11938 4195 M00056748C:B08 MA175:B05 AF054183gi|4092053|gb|AF054183.1AF054183 1.2E−165 Homo sapiens GTP bindingprotein mRNA, complete cds 4196 M00056749A:F01 MA175:C05 Y14736gi|2765422|emb|Y14736.1HSIGG1KL 1.2E−249 Homo sapiens mRNA forimmunoglobulin kappa light chain 4197 M00056754B:A10 MA175:G05 V00710gi|13683|emb|V00710.1MIT1HS Human 6.3E−292 mitochondrial genes forseveral tRNAs (Phe, Val, Leu) and 12S and 16S ribosomal RNAs 4198M00056754B:H06 MA175:H05 D38112 gi|644480|dbj|D38112.1HUMMTA Homo1.4E−252 sapiens mitochondrial DNA, complete sequence 4199RG:1653390:10014:E05 MA163:E05 M15353 gi|306486|gb|M15353.1HUMIF4E Homo1.5E−138 sapiens cap-binding protein mRNA, complete cds 4200RG:1669553:10014:G05 MA163:G05 X03663 gi|29899|emb|X03663.1HSCFMS Human5.8E−221 mRNA for c-fms proto-oncogene 4201 M00043355A:H12 MA183:B05M94314 gi|292436|gb|M94314.1HUMRPL30A 7.9E−66 Homo sapiens ribosomalprotein L30 mRNA, complete cds 4202 M00043355B:F10 MA183:C05 AK055653gi|16550433|dbj|AK055653.1AK055653 1.1E−165 Homo sapiens cDNA FLJ31091fis, clone IMR321000155, highly similar to 60S RIBOSOMAL PROTEIN L35A4203 M00043357B:B10 MA183:G05 NM_000978 gi|14591907|ref|NM_000978.2 Homo3.7E−206 sapiens ribosomal protein L23 (RPL23), mRNA 4204 M00054557C:D09MA185:G05 NM_012423 gi|14591905|ref|NM_012423.2 Homo 9.6E−167 sapiensribosomal protein L13a (RPL13A), mRNA 4205 M00043358B:G11 MA183:H05M60854 gi|338446|gb|M60854.1HUMSRAA 5.2E−280 Human ribosomal protein S16mRNA, complete cds 4206 M00043396D:B04 MA183:A11 AF026166gi|4090928|gb|AF026166.1AF026166 4.1E−237 Homo sapienschaperonin-containing TCP- 1 beta subunit homolog mRNA, complete cds4207 M00054612D:D11 MA185:H11 NM_006013 gi|15718685|ref|NM_006013.2 Homo1.2E−171 sapiens ribosomal protein L10 (RPL10), mRNA 4208 M00055409B:D08MA199:A05 BC016748 gi|16876941|gb|BC016748.1BC016748 3.6E−55 Homosapiens, ribosomal protein L37a, clone MGC: 26772 IMAGE: 4831278, mRNA,complete cds 4209 M00055409D:F06 MA199:B05 V00572gi|35434|emb|V00572.1HSPGK1 Human 1.6E−186 mRNA encodingphosphoglycerate kinase 4210 M00055410A:A06 MA199:C05 0.80422 4211M00056659A:D08 MA186:F05 M15470 gi|187680|gb|M15470.1HUMMHB44   3E−275Human MHC class I HLA-B44 mRNA, partial cds 4212 M00056704C:H08MA186:D11 BC001125 gi|12654578|gb|BC001125.1BC001125 8.2E−282 Homosapiens, peptidylprolyl isomerase B (cyclophilin B), clone MGC: 2224IMAGE: 2966791, mRNA, com 4213 M00055553C:B06 MA169:A06 4214M00056280B:D10 MA181:A06 0.72079 4215 M00056282D:G10 MA181:C06 0.05211AJ420520 gi|17066384|emb|AJ420520.1HSA420520 1.5E−88 Homo sapiens mRNAfull length insert cDNA clone EUROIMAGE 1979495 4216 M00056288B:A12MA181:G06 D14530 gi|414348|dbj|D14530.1HUMRSPT 9.8E−23 Human homolog ofyeast ribosomal protein S28, complete cds 4217 M00055686D:E11 MA169:B12L02785 gi|291963|gb|L02785.1HUMDRA Homo 5.9E−202 sapiens colonmucosa-associated (DRA) mRNA, complete cds 4218 M00042346B:F09 MA181:C120.23093 AK000168 gi|7020079|dbj|AK000168.1AK000168 7.4E−202 Homo sapienscDNA FLJ20161 fis, clone COL09252, highly similar to L33930 Homo sapiensCD24 signal 4219 M00055698C:E05 MA169:E12 0.82609 4220 M00042347C:D07MA181:E12 M12759 gi|532596|gb|M12759.1HUMIGJ02 3.2E−166 Human Ig J chaingene, exons 3 and 4 4221 M00055702C:C04 MA169:F12 0.85 4222M00042348C:F03 MA181:G12 X60489 gi|31099|emb|X60489.1HSEF1B Human6.8E−233 mRNA for elongation factor-1-beta 4223 M00055335D:E01 MA197:D06BC003510 gi|13097578|gb|BC003510.1BC003510 2.6E−176 Homo sapiens,prothymosin, alpha (gene sequence 28), clone MGC: 10549 IMAGE: 3610808,mRNA, complet 4224 M00056180C:E06 MA180:B06 BC018190gi|17390422|gb|BC018190.1BC018190 5.3E−171 Homo sapiens, Similar tometallothionein 1L, clone MGC: 9187 IMAGE: 3859643, mRNA, complete cds4225 M00056184B:G11 MA180:D06 Y00345 gi|35569|emb|Y00345.1HSPOLYAB8.2E−254 Human mRNA for polyA binding protein 4226 M00056514A:F06MA173:A12 AJ335311 gi|15879729|emb|AJ335311.1HSA335311 7.7E−54 Homosapiens genomic sequence surrounding NotI site, clone NR1-WB8C 4227M00056514C:H11 MA173:D12 BC000386 gi|12653234|gb|BC000386.1BC0003861.8E−242 Homo sapiens, eukaryotic translation initiation factor 3,subunit 3 (gamma, 40 kD), clone MGC: 8431 4228 M00054674D:C05 MA187:C06D14530 gi|414348|dbj|D14530.1HUMRSPT 8.3E−198 Human homolog of yeastribosomal protein S28, complete cds 4229 M00054675A:H07 MA187:D06 X00474gi|35706|emb|X00474.1HSPS2 Human pS2 7.8E−170 mRNA induced by estrogenfrom human breast cancer cell line MCF-7 4230 M00054878A:G12 MA189:D06AL359678 gi|15215911|emb|AL359678.15AL359678 2.4E−207 Human DNA sequencefrom clone RP11- 550J21 on chromosome 9, complete sequence [Homosapiens] 4231 M00054676B:D07 MA187:H06 BC000749gi|13879207|gb|BC000749.1BC000749 2.9E−129 Homo sapiens, lactatedehydrogenase A, clone MGC: 2417 IMAGE: 2960999, mRNA, complete cds 4232M00054725A:E09 MA187:B12 NM_022551 gi|14165467|ref|NM_022551.2 Homo2.7E−241 sapiens ribosomal protein S18 (RPS18), mRNA 4233 M00054924C:B09MA189:C12 0.63711 4234 M00054726D:B04 MA187:D12 X16064gi|37495|emb|X16064.1HSTUMP Human 1.1E−271 mRNA for translationallycontrolled tumor protein 4235 M00054927A:H09 MA189:E12 X06705gi|35511|emb|X06705.1HSPLAX Human 2.7E−297 PLA-X mRNA 4236M00054727C:F11 MA187:F12 0.7234 4237 M00054728A:H05 MA187:H12 X16064gi|37495|emb|X16064.1HSTUMP Human 1.3E−168 mRNA for translationallycontrolled tumor protein 4238 M00054930B:G05 MA189:H12 U15008gi|600747|gb|U15008.1HSU15008 Human   7E−270 SnRNP core protein Sm D2mRNA, complete cds 4239 M00057214C:G11 MA193:B06 U55206gi|2957143|gb|U55206.1HSU55206 Homo 4.1E−115 sapiens humangamma-glutamyl hydrolase (hGH) mRNA, complete cds 4240 M00057216C:G01MA193:D06 BC000695 gi|12653812|gb|BC000695.1BC000695 7.3E−28 Homosapiens, Similar to tetraspan 1, clone IMAGE: 3349380, mRNA 4241M00057217C:B07 MA193:F06 AK057120 gi|16552707|dbj|AK057120.1AK0571203.6E−206 Homo sapiens cDNA FLJ32558 fis, clone SPLEN1000143, highlysimilar to HIGH MOBILITY GROUP PROTEI 4242 M00042695A:H04 MA167:B06BC007075 gi|13937928|gb|BC007075.1BC007075 9.6E−37 Homo sapiens,hemoglobin, beta, clone MGC: 14540 IMAGE: 4292125, mRNA, complete cds4243 M00042695D:D09 MA167:C06 BC018749 gi|17511797|gb|BC018749.1BC0187493.5E−194 Homo sapiens, Similar to immunoglobulin lambda joining 3, cloneMGC: 31942 IMAGE: 4854511, mRNA, co 4244 M00042771A:D01 MA171:D06BC007659 gi|14043327|gb|BC007659.1BC007659 6.7E−239 Homo sapiens,diaphorase (NADH/NADPH) (cytochrome b-5 reductase), clone MGC: 2073IMAGE: 3349257, m 4245 M00042772D:F02 MA171:E06 NM_002295gi|9845501|ref|NM_002295.2 Homo 2.2E−254 sapiens laminin receptor 1 (67kD, ribosomal protein SA) (LAMR1), mRNA 4246 M00042773A:A12 MA171:F06AK000009 gi|7019813|dbj|AK000009.1AK000009 2.6E−213 Homo sapiens cDNAFLJ20002 fis, clone ADKA01577 4247 M00042699B:B10 MA167:G06 X98311gi|1524059|emb|X98311.1HSCGM2ANT 1.5E−31 H. sapiens mRNA forcarcinoembryonic antigen family member 2, CGM2 4248 M00042889A:H07MA167:A12 NM_005950 gi|10835229|ref|NM_005950.1 Homo   6E−202 sapiensmetallothionein 1G (MT1G), mRNA 4249 M00042819A:C09 MA171:A12 BC009220gi|14327996|gb|BC009220.1BC009220 5.2E−218 Homo sapiens, clone MGC:16362 IMAGE: 3927795, mRNA, complete cds 4250 M00042819C:B03 MA171:B12NM_000995 gi|16117786|ref|NM_000995.2 Homo 9.4E−207 sapiens ribosomalprotein L34 (RPL34), transcript variant 1, mRNA 4251 M00042895B:C02MA167:C12 AF217186 gi|11526786|gb|AF217186.1AF217186 1.4E−283 Homosapiens inorganic pyrophosphatase 1 (PPA1) mRNA, complete cds 4252M00042823B:A02 MA171:C12 AF212248 gi|13182770|gb|AF212248.1AF2122485.1E−252 Homo sapiens CDA09 mRNA, complete cds 4253 M00042895D:B04MA167:E12 U83908 gi|1825561|gb|U83908.1HSU83908 2.4E−229 Human nuclearantigen H731 mRNA, complete cds 4254 M00056564B:F11 MA174:F06 AL136593gi|7018431|emb|AL136593.1HSM801567 3.4E−284 Homo sapiens mRNA; cDNADKFZp761K102 (from clone DKFZp761K102); complete cds 4255 M00056564C:E08MA174:G06 Z74616 gi|1418929|emb|Z74616.1HSPPA2ICO 1.4E−286 H. sapiensmRNA for prepro-alpha2(I) collagen 4256 M00056615D:A01 MA174:A12 X12881gi|34036|emb|X12881.1HSKER18R 1.8E−273 Human mRNA for cytokeratin 184257 M00056620D:F02 MA174:G12 AK000335 gi|7020350|dbj|AK000335.1AK0003353.5E−287 Homo sapiens cDNA FLJ20328 fis, clone HEP10039 4258RG:359184:10009:A06 MA158:A06 M35663 gi|189505|gb|M35663.1HUMP68A Human1.6E−258 p68 kinase mRNA, complete cds 4259 RG:428530:10009:D12MA158:D12 AF321918 gi|12958659|gb|AF321918.1AF321918 0 Homo sapienstesticular acid phosphatase (ACPT) gene, complete cds, alternativelyspliced product 4260 M00057310A:A07 MA182:A06 AF054187gi|4092059|gb|AF054187.1AF054187 7.3E−143 Homo sapiens alpha NAC mRNA,complete cds 4261 M00054503C:H10 MA184:F06 BC018828gi|17402971|gb|BC018828.1BC018828   2E−276 Homo sapiens, clone IMAGE:3343539, mRNA 4262 M00043302C:D03 MA182:C12 BC006791gi|13905015|gb|BC006791.1BC006791 8.3E−282 Homo sapiens, ribosomalprotein L10a, clone MGC: 5203 IMAGE: 2901249, mRNA, complete cds 4263M00054535B:F10 MA184:F12 S35960 gi|249370|gb|S35960.1S35960 laminin4.1E−112 receptor homolog {3′ region} [human, mRNA Partial, 739 nt] 4264M00054535C:D10 MA184:G12 BC008063 gi|14165520|gb|BC008063.1BC0080634.7E−274 Homo sapiens, Similar to KIAA0102 gene product, clone MGC: 2249IMAGE: 2967488, mRNA, complete cds 4265 M00054535C:H09 MA184:H12AB020680 gi|4240234|dbj|AB020680.1AB020680 3.1E−275 Homo sapiens mRNAfor KIAA0873 protein, partial cds 4266 M00054964B:A08 MA198:C06 BC017189gi|16877928|gb|BC017189.1BC017189 1.1E−190 Homo sapiens, myo-inositol1-phosphate synthase A1, clone MGC: 726 IMAGE: 3140452, mRNA, complete c4267 M00054966C:H01 MA198:D06 BC018828 gi|17402971|gb|BC018828.1BC0188284.4E−190 Homo sapiens, clone IMAGE: 3343539, mRNA 4268 M00055022D:F01MA198:D12 NM_000975 gi|15431289|ref|NM_000975.2 Homo 2.5E−182 sapiensribosomal protein L11 (RPL11), mRNA 4269 M00055026C:C12 MA198:G12NM_007209 gi|16117792|ref|NM_007209.2 Homo   4E−184 sapiens ribosomalprotein L35 (RPL35), mRNA 4270 M00055027B:C11 MA198:H12 AF283772gi|10281741|gb|AF283772.2AF283772   1E−187 Homo sapiens clone TCBAP0781mRNA sequence 4271 M00055826D:C11 MA170:E12 0.7443 4272 M00055828C:D10MA170:G12 V00662 gi|13003|emb|V00662.1MIHSXX 9.5E−229 H. sapiensmitochondrial genome 4273 M00055828D:F12 MA170:H12 0.71968 BC001573gi|16306770|gb|BC001573.1BC001573 2.8E−37 Homo sapiens, clone MGC: 5522IMAGE: 3454199, mRNA, complete cds 4274 M00055215C:E11 MA196:B06BC001118 gi|12654566|gb|BC001118.1BC001118 2.4E−288 Homo sapiens,Similar to seven transmembrane domain protein, clone MGC: 1936 IMAGE:2989840, mRNA, 4275 M00055217C:E09 MA196:D06 BC010187gi|14603477|gb|BC010187.1BC010187 4.3E−215 Homo sapiens, ribosomalprotein S11, clone MGC: 20218 IMAGE: 4547934, mRNA, complete cds 4276M00055221B:C01 MA196:E06 NM_001016 gi|14277699|ref|NM_001016.2 Homo4.7E−246 sapiens ribosomal protein S12 (RPS12), mRNA 4277 M00055222A:E02MA196:G06 NM_000987 gi|17017970|ref|NM_000987.2 Homo 2.1E−226 sapiensribosomal protein L26 (RPL26), mRNA 4278 M00056226D:F03 MA180:B12BC011835 gi|15080118|gb|BC011835.1BC011835 1.7E−57 Homo sapiens, Similarto ATPase, Na+/K+ transporting, beta 3 polypeptide, clone MGC: 20152IMAGE: 3 4279 M00055258A:G02 MA196:F12 BC016753gi|16876954|gb|BC016753.1BC016753 1.3E−102 Homo sapiens, clone MGC: 1138IMAGE: 2987963, mRNA, complete cds 4280 M00055998A:A02 MA179:A06AF343729 gi|13649973|gb|AF343729.1AF343729 1.4E−283 Homo sapiens 3-alphahydroxysteroid dehydrogenase mRNA, complete cds 4281 M00056945A:B11MA177:A06 0.89778 4282 M00056945D:H03 MA177:C06 0.71282 4283M00056001A:F11 MA179:D06 BC015983 gi|16359036|gb|BC015983.1BC0159834.5E−165 Homo sapiens, clone IMAGE: 4074053, mRNA 4284 M00056946D:B04MA177:F06 AF028832 gi|3287488|gb|AF028832.1AF028832   1E−296 Homosapiens Hsp89-alpha-delta-N mRNA, complete cds 4285 M00056101B:B02MA179:A12 AL049999 gi|4884252|emb|AL049999.1HSM800347   3E−100 Homosapiens mRNA; cDNA DKFZp564M182 (from clone DKFZp564M182); partial cds4286 M00056110C:D09 MA179:E12 AK024903gi|10437317|dbj|AK024903.1AK024903   1E−209 Homo sapiens cDNA: FLJ21250fis, clone COL01253, highly similar to AB020527 Homo sapiens mRNA fo4287 M00056111B:H03 MA179:F12 0.81436 4288 M00054772B:H06 MA188:G06L19185 gi|440307|gb|L19185.1HUMNKEFB 3.6E−178 Human natural killer cellenhancing factor (NKEFB) mRNA, complete cds 4289 M00054825B:B05MA188:C12 0.09038 NM_005348 gi|13129149|ref|NM_005348.1 Homo 4.1E−222sapiens heat shock 90 kD protein 1, alpha (HSPCA), mRNA 4290M00054831A:G04 MA188:D12 AL359585 gi|8655645|emb|AL359585.1HSM8026876.2E−116 Homo sapiens mRNA; cDNA DKFZp762B195 (from clone DKFZp762B195)4291 M00054831D:B07 MA188:F12 U43701 gi|1399085|gb|U43701.1HSU437014.2E−296 Human ribosomal protein L23a mRNA, complete cds 4292M00042862D:A12 MA172:B06 BC007097 gi|13937968|gb|BC007097.1BC0070971.9E−248 Homo sapiens, tissue inhibitor of metalloproteinase 1(erythroid potentiating activity, collagena 4293 M00042864A:E05MA172:E06 0.59184 4294 M00042864D:E06 MA172:F06 NM_007099gi|6005987|ref|NM_007099.1 Homo 3.5E−228 sapiens acid phosphatase 1,soluble (ACP1), transcript variant b, mRNA 4295 M00055514B:A05 MA168:E12BC001190 gi|12654700|gb|BC001190.1BC001190 1.4E−230 Homo sapiens,Similar to creatine kinase, brain, clone MGC: 3160 IMAGE: 3354679, mRNA,complete cds 4296 M00056763B:A12 MA175:D06 NM_004417gi|7108342|ref|NM_004417.2 Homo 6.4E−267 sapiens dual specificityphosphatase 1 (DUSP1), mRNA 4297 M00056767D:F06 MA175:F06 AF203815gi|6979641|gb|AF203815.1AF203815 8.6E−285 Homo sapiens alpha genesequence 4298 M00056821A:D08 MA175:A12 NM_001016gi|14277699|ref|NM_001016.2 Homo 8.3E−220 sapiens ribosomal protein S12(RPS12), mRNA 4299 M00056822C:G03 MA175:C12 NM_000970gi|16753226|ref|NM_000970.2 Homo 3.4E−284 sapiens ribosomal protein L6(RPL6), mRNA 4300 M00056823D:H02 MA175:E12 BC018828gi|17402971|gb|BC018828.1BC018828 1.9E−276 Homo sapiens, clone IMAGE:3343539, mRNA 4301 RG:1609994:10014:A06 MA163:A06 BC006322gi|13623444|gb|BC006322.1BC006322   1E−300 Homo sapiens, activatingtranscription factor 3, clone MGC: 12746 IMAGE: 4138076, mRNA, completecd 4302 RG:1667183:10014:F12 MA163:F12 BC000013gi|12652546|gb|BC000013.1BC000013 5.4E−58 Homo sapiens, insulin-likegrowth factor binding protein 3, clone MGC: 2305 IMAGE: 3506666, mRNA, c4303 M00043358D:C06 MA183:A06 AF113008 gi|6642739|gb|AF113008.1AF1130081.5E−152 Homo sapiens clone FLB0708 mRNA sequence 4304 M00054558B:E05MA185:A06 0.69811 BC014498 gi|15680272|gb|BC014498.1BC014498 1.1E−27Homo sapiens, clone IMAGE: 4856273, mRNA 4305 M00043361B:G03 MA183:E06NM_001025 gi|14790142|ref|NM_001025.2 Homo 1.3E−218 sapiens ribosomalprotein S23 (RPS23), mRNA 4306 M00043408C:D11 MA183:G12 U14967gi|550014|gb|U14967.1HSU14967 Human 1.4E−283 ribosomal protein L21 mRNA,complete cds 4307 M00054632A:E11 MA185:H12 0.18764 X73459gi|313660|emb|X73459.1HSSRP14A   2E−140 H. sapiens mRNA for signalrecognition particle subunit 14 4308 M00056661A:G05 MA186:A06 L18960gi|306724|gb|L18960.1HUMEIF4C Human 5.2E−280 protein synthesis factor(eIF-4C) mRNA, complete cds 4309 M00056661C:C11 MA186:B06 S72481gi|632789|gb|S72481.1S72481 pantophysin 3.4E−281 [human, keratinocyteline HaCaT, mRNA, 2106 nt] 4310 M00055412D:E05 MA199:B06 M26697gi|189311|gb|M26697.1HUMNUMB23 8.9E−176 Human nucleolar protein (B23)mRNA, complete cds 4311 M00055413A:G12 MA199:C06 BC012354gi|15214456|gb|BC012354.1BC012354 1.9E−95 Homo sapiens, clone MGC: 20390IMAGE: 4564801, mRNA, complete cds 4312 M00055414D:A09 MA199:D06 X06705gi|35511|emb|X06705.1HSPLAX Human 4.1E−187 PLA-X mRNA 4313M00056707B:C01 MA186:C12 AF178581 gi|10800410|gb|AF178581.2AF1785811.3E−252 Homo sapiens nasopharyngeal carcinoma gene sequence 4314M00056237D:C10 MA181:D01 0.64821 4315 M00056238B:D03 MA181:E01 AF083241gi|5106776|gb|AF083241.1HSPC024 9.4E−257 Homo sapiens HSPC024 mRNA,complete cds 4316 M00056239B:D05 MA181:G01 0.89873 4317 M00056241B:H07MA181:H01 0.625 NM_033340 gi|15718701|ref|NM_033340.1 Homo 2.2E−50sapiens caspase 7, apoptosis-related cysteine protease (CASP7),transcript variant beta, mRNA 4318 I:2921194:04B02:C06 MA118:C06AB006780 gi|2385451|dbj|AB006780.1AB006780 3.1E−222 Homo sapiens mRNAfor galectin-3, complete cds 4319 I:1624865:04B02:G06 MA118:G06 U15009gi|600749|gb|U15009.1HSU15009 Human 4.7E−246 SnRNP core protein Sm D3mRNA, complete cds 4320 I:1728607:04A02:H06 MA116:H06 BC016164gi|16740573|gb|BC016164.1BC016164   1E−262 Homo sapiens, small induciblecytokine subfamily D (Cys-X3-Cys), member 1 (fractalkine, neurotact 4321I:2827453:04B02:H06 MA118:H06 U27143 gi|862932|gb|U27143.1HSU27143 Human2.5E−113 protein kinase C inhibitor-I cDNA, complete cds 4322I:2070593:04B02:D12 MA118:D12 D83004 gi|1181557|dbj|D83004.1D83004 Human1.5E−233 epidermoid carcinoma mRNA for ubiquitin-conjugating enzyme E2similar to Drosophila bendless ge 4323 I:2683114:04A02:H12 MA116:H12L20493 gi|306754|gb|L20493.1HUMGAGLUTD   1E−300 Human gamma-glutamyltranspeptidase mRNA, complete cds 4324 I:1809336:02A02:G06 MA108:G06U09117 gi|483919|gb|U09117.1HSU09117 Human 1.3E−280 phospholipase cdelta 1 mRNA, complete cds

Example 50 Detection of Differential Expression Using Arrays

cDNA probes were prepared from total RNA isolated from the patient cellsdescribed above. Since LCM provides for the isolation of specific celltypes to provide a substantially homogenous cell sample, this providedfor a similarly pure RNA sample.

Total RNA was first reverse transcribed into cDNA using a primercontaining a T7 RNA polymerase promoter, followed by second strand DNAsynthesis. cDNA was then transcribed in vitro to produce antisense RNAusing the T7 promoter-mediated expression (see, e.g., Luo et al. (1999)Nature Med 5:117-122), and the antisense RNA was then converted intocDNA. The second set of cDNAs were again transcribed in vitro, using theT7 promoter, to provide antisense RNA. Optionally, the RNA was againconverted into cDNA, allowing for up to a third round of T7-mediatedamplification to produce more antisense RNA. Thus the procedure providedfor two or three rounds of in vitro transcription to produce the finalRNA used for fluorescent labeling.

Fluorescent probes were generated by first adding control RNA to theantisense RNA mix, and producing fluorescently labeled cDNA from the RNAstarting material. Fluorescently labeled cDNAs prepared from the tumorRNA sample were compared to fluorescently labeled cDNAs prepared fromnormal cell RNA sample. For example, the cDNA probes from the normalcells were labeled with Cy3 fluorescent dye (green) and the cDNA probesprepared from the tumor cells were labeled with Cy5 fluorescent dye(red), and vice versa.

Each array used had an identical spatial layout and control spot set.Each microarray was divided into two areas, each area having an arraywith, on each half, twelve groupings of 32×12 spots, for a total ofabout 9,216 spots on each array. The two areas are spotted identicallywhich provide for at least two duplicates of each clone per array.

Polynucleotides for use on the arrays were obtained from both publiclyavailable sources and from cDNA libraries generated from selected celllines and patient tissues as described above and in Table 31. PCRproducts of from about 0.5 kb to 2.0 kb amplified from these sourceswere spotted onto the array using a Molecular Dynamics Gen III spotteraccording to the manufacturer's recommendations. The first row of eachof the 24 regions on the array had about 32 control spots, including 4negative control spots and 8 test polynucleotides. The testpolynucleotides were spiked into each sample before the labelingreaction with a range of concentrations from 2-600 pg/slide and ratiosof 1:1. For each array design, two slides were hybridized with the testsamples reverse-labeled in the labeling reaction. This provided forabout four duplicate measurements for each clone, two of one color andtwo of the other, for each sample.

The differential expression assay was performed by mixing equal amountsof probes from tumor cells and normal cells of the same patient. Thearrays were prehybridized by incubation for about 2 hrs at 60° C. in5×SSC/0.2% SDS/1 mM EDTA, and then washed three times in water and twicein isopropanol. Following prehybridization of the array, the probemixture was then hybridized to the array under conditions of highstringency (overnight at 42° C. in 50% formamide, 5×SSC, and 0.2% SDS.After hybridization, the array was washed at 55° C. three times asfollows: 1) first wash in 1×SSC/0.2% SDS; 2) second wash in 0.1×SSC/0.2%SDS; and 3) third wash in 0.1×SSC.

The arrays were then scanned for green and red fluorescence using aMolecular Dynamics Generation III dual color laser-scanner/detector. Theimages were processed using BioDiscovery Autogene software, and the datafrom each scan set normalized to provide for a ratio of expressionrelative to normal. Data from the microarray experiments was analyzedaccording to the algorithms described in U.S. application Ser. No.60/252,358, filed Nov. 20, 2000, by E. J. Moler, M. A. Boyle, and F. M.Randazzo, and entitled “Precision and accuracy in cDNA microarray data,”which application is specifically incorporated herein by reference.

The experiment was repeated, this time labeling the two probes with theopposite color in order to perform the assay in both “color directions.”Each experiment was sometimes repeated with two more slides (one in eachcolor direction). The level fluorescence for each sequence on the arrayexpressed as a ratio of the geometric mean of 8 replicate spots/genesfrom the four arrays or 4 replicate spots/gene from 2 arrays or someother permutation. The data were normalized using the spiked positivecontrols present in each duplicated area, and the precision of thisnormalization was included in the final determination of thesignificance of each differential. The fluorescent intensity of eachspot was also compared to the negative controls in each duplicated areato determine which spots have detected significant expression levels ineach sample.

A statistical analysis of the fluorescent intensities was applied toeach set of duplicate spots to assess the precision and significance ofeach differential measurement, resulting in a p-value testing the nullhypothesis that there is no differential in the expression level betweenthe tumor and normal samples of each patient. During initial analysis ofthe microarrays, the hypothesis was accepted if p>10⁻³, and thedifferential ratio was set to 1.000 for those spots. All other spotshave a significant difference in expression between the tumor and normalsample. If the tumor sample has detectable expression and the normaldoes not, the ratio is truncated at 1000 since the value for expressionin the normal sample would be zero, and the ratio would not be amathematically useful value (e.g., infinity). If the normal sample hasdetectable expression and the tumor does not, the ratio is truncated to0.001, since the value for expression in the tumor sample would be zeroand the ratio would not be a mathematically useful value. These lattertwo situations are referred to herein as “on/off.” Database tables werepopulated using a 95% confidence level (p>0.05).

Table 33 provides the results for gene products that were expressed byat least 2-fold or greater in the colon tumor samples relative to normaltissue samples in at least 20% of the patients tested, or gene productsin which expression levels of the gene in colon tumor cells was lessthan or equal to ½ of the expression level in normal tissue samples inat least 20% of the patients tested. Table 33 includes: (1) the “SEQ IDNO” of the sequence tested; (2) the spot identification number (“SpotID”); (3) the “Clone ID” assigned to the clone from which the sequencewas isolated; (4) the “MACIone ID” assigned to the clone from which thesequence was isolated; (5) the percentage of patients tested in whichexpression levels (e.g., as message level) of the gene was at least2-fold greater in cancerous tissue than in matched normal tissue(“>=2×”); (6) the percentage of patients tested in which expressionlevels (e.g., as message level) of the gene was at least 5-fold greaterin cancerous tissue than in matched normal tissue (“>=5×”); (7) thepercentage of patients tested in which expression levels (e.g., asmessage level) of the gene was less than or equal to ½ of the expressionlevel in matched normal cells (“<=half×”); and (8) the number ofpatients analyzed (“Num Ratios”).

Table 33 also includes the results from each patient, identified by thepatient ID number (e.g., 10). This data represents the ratio ofdifferential expression for the samples tested from that particularpatient's tissues (e.g., “10” is the ratio from the tissue samples ofPatient ID no. 10). The ratios of differential expression are expressedas a normalized hybridization signal associated with the tumor probedivided by the normalized hybridization signal with the normal probe.Thus, a ratio greater than 1 indicates that the gene product isincreased in expression in cancerous cells relative to normal cells,while a ratio of less than 1 indicates the opposite.

These data provide evidence that the genes represented by thepolynucleotides having the indicated sequences are differentiallyexpressed in colon cancer as compared to normal non-cancerous colontissue.

Example 51 Antisense Regulation of Gene Expression

The expression of the differentially expressed genes represented by thepolynucleotides in the cancerous cells can be analyzed using antisenseknockout technology to confirm the role and function of the gene productin tumorigenesis, e.g., in promoting a metastatic phenotype.

A number of different oligonucleotides complementary to the mRNAgenerated by the differentially expressed genes identified herein can bedesigned as potential antisense oligonucleotides, and tested for theirability to suppress expression of the genes. Sets of antisense oligomersspecific to each candidate target are designed using the sequences ofthe polynucleotides corresponding to a differentially expressed gene andthe software program HYBsimulator Version 4 (available for Windows95/Windows NT or for Power Macintosh, RNAture, Inc. 1003 Health SciencesRoad, West, Irvine, Calif. 92612 USA). Factors that are considered whendesigning antisense oligonucleotides include: 1) the secondary structureof oligonucleotides; 2) the secondary structure of the target gene; 3)the specificity with no or minimum cross-hybridization to otherexpressed genes; 4) stability; 5) length and 6) terminal GC content. Theantisense oligonucleotide is designed so that it will hybridize to itstarget sequence under conditions of high stringency at physiologicaltemperatures (e.g., an optimal temperature for the cells in culture toprovide for hybridization in the cell, e.g., about 37° C.), but withminimal formation of homodimers.

Using the sets of oligomers and the HYB simulator program, three to tenantisense oligonucleotides and their reverse controls are designed andsynthesized for each candidate mRNA transcript, which transcript isobtained from the gene corresponding to the target polynucleotidesequence of interest. Once synthesized and quantitated, the oligomersare screened for efficiency of a transcript knock-out in a panel ofcancer cell lines. The efficiency of the knock-out is determined byanalyzing mRNA levels using lightcycler quantification. The oligomersthat resulted in the highest level of transcript knock-out, wherein thelevel was at least about 50%, preferably about 80-90%, up to 95% or moreup to undetectable message, are selected for use in a cell-basedproliferation assay, an anchorage independent growth assay, and anapoptosis assay.

The ability of each designed antisense oligonucleotide to inhibit geneexpression is tested through transfection into SW620 colon carcinomacells. For each transfection mixture, a carrier molecule (such as alipid, lipid derivative, lipid-like molecule, cholesterol, cholesterolderivative, or cholesterol-like molecule) is prepared to a workingconcentration of 0.5 mM in water, sonicated to yield a uniform solution,and filtered through a 0.45 μm PVDF membrane. The antisense or controloligonucleotide is then prepared to a working concentration of 100 μM insterile Millipore water. The oligonucleotide is further diluted inOptiMEM™ (Gibco/BRL), in a microfuge tube, to 2 μM, or approximately 20μg oligo/ml of OptiMEM™. In a separate microfuge tube, the carriermolecule, typically in the amount of about 1.5-2 nmol carrier/μgantisense oligonucleotide, is diluted into the same volume of OptiMEM™used to dilute the oligonucleotide. The diluted antisenseoligonucleotide is immediately added to the diluted carrier and mixed bypipetting up and down. Oligonucleotide is added to the cells to a finalconcentration of 30 nM.

The level of target mRNA that corresponds to a target gene of interestin the transfected cells is quantitated in the cancer cell lines usingthe Roche LightCycler™ real-time PCR machine. Values for the target mRNAare normalized versus an internal control (e.g., beta-actin). For each20 μl reaction, extracted RNA (generally 0.2-1 μg total) is placed intoa sterile 0.5 or 1.5 ml microcentrifuge tube, and water is added to atotal volume of 12.5 μl. To each tube is added 7.5 μl of a buffer/enzymemixture, prepared by mixing (in the order listed) 2.5 μl H₂O, 2.0 μl 10×reaction buffer, 10 μl oligo dT (20 μmol), 1.0 μl dNTP mix (10 mM each),0.5 μl RNAsin® (20 u) (Ambion, Inc., Hialeah, Fla.), and 0.5 μl MMLVreverse transcriptase (50 u) (Ambion, Inc.). The contents are mixed bypipetting up and down, and the reaction mixture is incubated at 42° C.for 1 hour. The contents of each tube are centrifuged prior toamplification.

An amplification mixture is prepared by mixing in the following order:1×PCR buffer II, 3 mM MgCl₂, 140 μM each dNTP, 0.175 μmol each oligo,1:50,000 dil of SYBR® Green, 0.25 mg/ml BSA, 1 unit Taq polymerase, andH₂O to 20 (PCR buffer II is available in 10× concentration fromPerkin-Elmer, Norwalk, Conn.). In 1× concentration it contains 10 mMTris pH 8.3 and 50 mM KCl. SYBR® Green (Molecular Probes, Eugene, Oreg.)is a dye which fluoresces when bound to double stranded DNA. As doublestranded PCR product is produced during amplification, the fluorescencefrom SYBR® Green increases. To each 20 μl aliquot of amplificationmixture, 2 μl of template RT is added, and amplification is carried outaccording to standard protocols. The results are expressed as thepercent decrease in expression of the corresponding gene productrelative to non-transfected cells, vehicle-only transfected(mock-transfected) cells, or cells transfected with reverse controloligonucleotides.

Example 52 Effect of Expression on Proliferation

The effect of gene expression on the inhibition of cell proliferationcan be assessed in metastatic breast cancer cell lines (MDA-MB-231(“231”)); SW620 colon colorectal carcinoma cells; SKOV3 cells (a humanovarian carcinoma cell line); or LNCaP, PC3, 22Rv1, MDA-PCA-2b, or DU145prostate cancer cells.

Cells are plated to approximately 60-80% confluency in 96-well dishes.Antisense or reverse control oligonucleotide is diluted to 2 μM inOptiMEM™. The oligonucleotide-OptiMEM™ can then be added to a deliveryvehicle, which delivery vehicle can be selected so as to be optimizedfor the particular cell type to be used in the assay. The oligo/deliveryvehicle mixture is then further diluted into medium with serum on thecells. The final concentration of oligonucleotide for all experimentscan be about 300 nM.

Antisense oligonucleotides are prepared as described above (see Example51). Cells are transfected overnight at 37° C. and the transfectionmixture is replaced with fresh medium the next morning. Transfection iscarried out as described above in Example 51.

Those antisense oligonucleotides that result in inhibition ofproliferation of SW620 cells indicate that the corresponding gene playsa role in production or maintenance of the cancerous phenotype incancerous colon cells. Those antisense oligonucleotides that inhibitproliferation in SKOV3 cells represent genes that play a role inproduction or maintenance of the cancerous phenotype in cancerous breastcells. Those antisense oligonucleotides that result in inhibition ofproliferation of MDA-MB-231 cells indicate that the corresponding geneplays a role in production or maintenance of the cancerous phenotype incancerous ovarian cells. Those antisense oligonucleotides that inhibitproliferation in LNCaP, PC3, 22Rv1, MDA-PCA-2b, or DU145 cells representgenes that play a role in production or maintenance of the cancerousphenotype in cancerous prostate cells.

Example 53 Effect of Gene Expression on Cell Migration

The effect of gene expression on the inhibition of cell migration can beassessed in SW620 colon cancer cells using static endothelial cellbinding assays, non-static endothelial cell binding assays, andtransmigration assays.

For the static endothelial cell binding assay, antisenseoligonucleotides are prepared as described above (see Example 51). Twodays prior to use, colon cancer cells (CaP) are plated and transfectedwith antisense oligonucleotide as described above (see Examples 51 and52). On the day before use, the medium is replaced with fresh medium,and on the day of use, the medium is replaced with fresh mediumcontaining 2 μM CellTracker green CMFDA (Molecular Probes, Inc.) andcells are incubated for 30 min. Following incubation, CaP medium isreplaced with fresh medium (no CMFDA) and cells are incubated for anadditional 30-60 min. CaP cells are detached using CMF PBS/2.5 mM EDTAor trypsin, spun and resuspended in DMEM/1% BSA/10 mM HEPES pH 7.0.Finally, CaP cells are counted and resuspended at a concentration of1×10⁶ cells/ml.

Endothelial cells (EC) are plated onto 96-well plates at 40-50%confluence 3 days prior to use. On the day of use, EC are washed 1× withPBS and 50λ DMDM/1% BSA/10 mM HEPES pH 7 is added to each well. To eachwell is then added 50K (50λ) CaP cells in DMEM/1% BSA/10 mM HEPES pH 7.The plates are incubated for an additional 30 min and washed 5× with PBScontaining Ca⁺⁺ and Mg⁺⁺. After the final wash, 100 μL PBS is added toeach well and fluorescence is read on a fluorescent plate reader(Ab492/Em 516 nm).

For the non-static endothelial cell binding assay, CaP are prepared asdescribed above. EC are plated onto 24-well plates at 30-40% confluence3 days prior to use. On the day of use, a subset of EC are treated withcytokine for 6 hours then washed 2× with PBS. To each well is then added150-200K CaP cells in DMEM/1% BSA/10 mM HEPES pH 7. Plates are placed ona rotating shaker (70 RPM) for 30 min and then washed 3× with PBScontaining Ca⁺⁺ and Mg⁺⁺. After the final wash, 500 μL PBS is added toeach well and fluorescence is read on a fluorescent plate reader(Ab492/Em 516 nm).

For the transmigration assay, CaP are prepared as described above withthe following changes. On the day of use, CaP medium is replaced withfresh medium containing 5 μM CellTracker green CMFDA (Molecular Probes,Inc.) and cells are incubated for 30 min. Following incubation, CaPmedium is replaced with fresh medium (no CMFDA) and cells are incubatedfor an additional 30-60 min. CaP cells are detached using CMF PBS/2.5 mMEDTA or trypsin, spun and resuspended in EGM-2-MV medium. Finally, CaPcells are counted and resuspended at a concentration of 1×10⁶ cells/ml.

EC are plated onto FluorBlok transwells (BD Biosciences) at 30-40%confluence 5-7 days before use. Medium is replaced with fresh medium 3days before use and on the day of use. To each transwell is then added50K labeled CaP. 30 min prior to the first fluorescence reading, 10 μgof FITC-dextran (10K MW) is added to the EC plated filter. Fluorescenceis then read at multiple time points on a fluorescent plate reader(Ab492/Em 516 nm).

Those antisense oligonucleotides that result in inhibition of binding ofSW620 colon cancer cells to endothelial cells indicate that thecorresponding gene plays a role in the production or maintenance of thecancerous phenotype in cancerous colon cells. Those antisenseoligonucleotides that result in inhibition of endothelial celltransmigration by SW620 colon cancer cells indicate that thecorresponding gene plays a role in the production or maintenance of thecancerous phenotype in cancerous colon cells.

Example 54 Effect of Gene Expression on Colony Formation

The effect of gene expression upon colony formation of SW620 cells,SKOV3 cells, MD-MBA-231 cells, LNCaP cells, PC3 cells, 22Rv1 cells,MDA-PCA-2b cells, and DU145 cells can be tested in a soft agar assay.Soft agar assays are conducted by first establishing a bottom layer of 2ml of 0.6% agar in media plated fresh within a few hours of layering onthe cells. The cell layer is formed on the bottom layer by removingcells transfected as described above from plates using 0.05% trypsin andwashing twice in media. The cells are counted in a Coulter counter, andresuspended to 10⁶ per ml in media. 10 μl aliquots are placed with mediain 96-well plates (to check counting with WST1), or diluted further forthe soft agar assay. 2000 cells are plated in 800 μl 0.4% agar induplicate wells above 0.6% agar bottom layer. After the cell layer agarsolidifies, 2 ml of media is dribbled on top and antisense or reversecontrol oligo (produced as described in Example S1) is added withoutdelivery vehicles. Fresh media and oligos are added every 3-4 days.Colonies form in 10 days to 3 weeks. Fields of colonies are counted byeye. Wst-1 metabolism values can be used to compensate for smalldifferences in starting cell number. Larger fields can be scanned forvisual record of differences.

Those antisense oligonucleotides that result in inhibition of colonyformation of SW620 cells indicate that the corresponding gene plays arole in production or maintenance of the cancerous phenotype incancerous colon cells. Those antisense oligonucleotides that inhibitcolony formation in SKOV3 cells represent genes that play a role inproduction or maintenance of the cancerous phenotype in cancerous breastcells. Those antisense oligonucleotides that result in inhibition ofcolony formation of MDA-MB-231 cells indicate that the correspondinggene plays a role in production or maintenance of the cancerousphenotype in cancerous ovarian cells. Those antisense oligonucleotidesthat inhibit colony formation in LNCaP, PC3, 22Rv1, MDA-PCA-2b, or DU145cells represent genes that play a role in production or maintenance ofthe cancerous phenotype in cancerous prostate cells.

Example 55 Induction of Cell Death Upon Depletion of Polypeptides byDepletion of mRNA (“Antisense Knockout”)

In order to assess the effect of depletion of a target message upon celldeath, SW620 cells, or other cells derived from a cancer of interest,can be transfected for proliferation assays. For cytotoxic effect in thepresence of cisplatin (cis), the same protocol is followed but cells areleft in the presence of 2 μM drug. Each day, cytotoxicity is monitoredby measuring the amount of LDH enzyme released in the medium due tomembrane damage. The activity of LDH is measured using the CytotoxicityDetection Kit from Roche Molecular Biochemicals. The data is provided asa ratio of LDH released in the medium vs. the total LDH present in thewell at the same time point and treatment (rLDH/tLDH). A positivecontrol using antisense and reverse control oligonucleotides for BCL2 (aknown anti-apoptotic gene) is included; loss of message for BCL2 leadsto an increase in cell death compared with treatment with the controloligonucleotide (background cytotoxicity due to transfection).

Example 56 Functional Analysis of Gene Products Differentially Expressedin Colon Cancer in Patients

The gene products of sequences of a gene differentially expressed incancerous cells can be further analyzed to confirm the role and functionof the gene product in tumorigenesis, e.g., in promoting or inhibitingdevelopment of a metastatic phenotype. For example, the function of geneproducts corresponding to genes identified herein can be assessed byblocking function of the gene products in the cell. For example, wherethe gene product is secreted or associated with a cell surface membrane,blocking antibodies can be generated and added to cells to examine theeffect upon the cell phenotype in the context of, for example, thetransformation of the cell to a cancerous, particularly a metastatic,phenotype. In order to generate antibodies, a clone corresponding to aselected gene product is selected, and a sequence that represents apartial or complete coding sequence is obtained. The resulting clone isexpressed, the polypeptide produced isolated, and antibodies generated.The antibodies are then combined with cells and the effect upontumorigenesis assessed.

Where the gene product of the differentially expressed genes identifiedherein exhibits sequence homology to a protein of known function (e.g.,to a specific kinase or protease) and/or to a protein family of knownfunction (e.g., contains a domain or other consensus sequence present ina protease family or in a kinase family), then the role of the geneproduct in tumorigenesis, as well as the activity of the gene product,can be examined using small molecules that inhibit or enhance functionof the corresponding protein or protein family.

Additional functional assays include, but are not necessarily limitedto, those that analyze the effect of expression of the correspondinggene upon cell cycle and cell migration. Methods for performing suchassays are well known in the art.

Example 57 Contig Assembly and Additional Gene Characterization

The sequences of the polynucleotides provided in the present inventioncan be used to extend the sequence information of the gene to which thepolynucleotides correspond (e.g., a gene, or mRNA encoded by the gene,having a sequence of the polynucleotide described herein). This expandedsequence information can in turn be used to further characterize thecorresponding gene, which in turn provides additional information aboutthe nature of the gene product (e.g., the normal function of the geneproduct). The additional information can serve to provide additionalevidence of the gene product's use as a therapeutic target, and providefurther guidance as to the types of agents that can modulate itsactivity.

In one example, a contig is assembled using a sequence of apolynucleotide of the present invention, which is present in a clone. A“contig” is a contiguous sequence of nucleotides that is assembled fromnucleic acid sequences having overlapping (e.g., shared or substantiallysimilar) sequence information. The sequences of publicly-available ESTs(Expressed Sequence Tags) and the sequences of various clones fromseveral cDNA libraries synthesized at Chiron can be used in the contigassembly.

The contig is assembled using the software program Sequencher, version4.05, according to the manufacturer's instructions and an overviewalignment of the contiged sequences is produced. The sequenceinformation obtained in the contig assembly can then be used to obtain aconsensus sequence derived from the contig using the Sequencher program.The consensus sequence is used as a query sequence in a TeraBLASTNsearch of the DGTI DoubleTwist Gene Index (DoubleTwist, Inc., Oakland,Calif.), which contains all the EST and non-redundant sequence in publicdatabases.

Through contig assembly and the use of homology searching softwareprograms, the sequence information provided herein can be readilyextended to confirm, or confirm a predicted, gene having the sequence ofthe polynucleotides described in the present invention. Further theinformation obtained can be used to identify the function of the geneproduct of the gene corresponding to the polynucleotides describedherein. While not necessary to the practice of the invention,identification of the function of the corresponding gene, can provideguidance in the design of therapeutics that target the gene to modulateits activity and modulate the cancerous phenotype (e.g., inhibitmetastasis, proliferation, and the like).

Example 58 Source of Biological Materials

The biological materials used in the experiments that led to the presentinvention are described below.

Source of Patient Tissue Samples

Normal and cancerous tissues were collected from patients using lasercapture microdissection (LCM) techniques, which techniques are wellknown in the art (see, e.g., Ohyama et al. (2000) Biotechniques29:530-6; Curran et al. (2000) Mol. Pathol. 53:64-8; Suarez-Quian et al.(1999) Biotechniques 26:328-35; Simone et al. (1998) Trends Genet.14:272-6; Conia et al. (1997) J. Clin. Lab. Anal. 11:28-38; Emmert-Bucket al. (1996) Science 274:998-1001). Table 34 provides information abouteach patient from which colon tissue samples were isolated, including:the Patient ID (“PT ID”) and Path ReportID (“Path ID”), which arenumbers assigned to the patient and the pathology reports foridentification purposes; the group (“Grp”) to which the patients havebeen assigned; the anatomical location of the tumor (“Anatom Loc”); theprimary tumor size (“Size”); the primary tumor grade (“Grade”); theidentification of the histopathological grade (“Histo Grade”); adescription of local sites to which the tumor had invaded (“LocalInvasion”); the presence of lymph node metastases (“Lymph Met”); theincidence of lymph node metastases (provided as a number of lymph nodespositive for metastasis over the number of lymph nodes examined) (“LymphMet Incid”); the regional lymphnode grade (“Reg Lymph Grade”); theidentification or detection of metastases to sites distant to the tumorand their location (“Dist Met & Loc”); the grade of distant metastasis(“Dist Met Grade”); and general comments about the patient or the tumor(“Comments”). Histopathology of all primary tumors indicated the tumorwas adenocarcinoma except for Patient ID Nos. 130 (for which noinformation was provided), 392 (in which greater than 50% of the cellswere mucinous carcinoma), and 784 (adenosquamous carcinoma). Extranodalextensions were described in three patients, Patient ID Nos. 784, 789,and 791. Lymphovascular invasion was described in Patient ID Nos. 128,228, 278, 517, 534, 784, 786, 789, 791, 890, and 892. Crohn's-likeinfiltrates were described in seven patients, Patient ID Nos. 52, 264,268, 392, 393, 784, and 791.

TABLE 34 Path Anatom Histo Pt ID ID Grp Loc Size Grade Grade LocalInvasion  10 16 III Cecum 8.5 T3 G2 through muscularis propriaapproaching pericolic fat, but not at serosal surface  15 21 IIIAscending 4.0 T3 G2 Extending into colon subserosal adipose tissue  5271 II Cecum 9.0 T3 G3 Invasion through muscularis propria, subserosalinvolvement; ileocec. valve involvement 121 140 II Sigmoid 6 T4 G2Invasion of muscularis propria into serosa, involving submucosa ofurinary bladder 125 144 II Cecum 6 T3 G2 Invasion through the muscularispropria into suserosal adipose tissue. Ileocecal junction. 128 147 IIITransverse 5.0 T3 G2 Invasion of colon muscularis propria intopercolonic fat 130 149 Splenic 5.5 T3 through wall and flexure intosurrounding adipose tissue 133 152 II Rectum 5.0 T3 G2 Invasion throughmuscularis propria into non- peritonealized pericolic tissue; grossconfiguration is annular. 141 160 IV Cecum 5.5 T3 G2 Invasion ofmuscularis propria into pericolonic adipose tissue, but not throughserosa. Arising from tubular adenoma. 156 175 III Hepatic 3.8 T3 G2Invasion through flexure mucsularis propria into subserosa/pericolicadipose, no serosal involvement. Gross configuration annular. 228 247III Rectum 5.8 T3 G2 to Invasion through G3 muscularis propria toinvolve subserosal, perirectoal adipose, and serosa 264 283 II Ascending5.5 T3 G2 Invasion through colon muscularis propria into subserosaladipose tissue. 266 285 III Transverse 9 T3 G2 Invades through colonmuscularis propria to involve pericolonic adipose, extends to serosa.267 286 III Ileocecal 4.5 T2 G2 Confined to muscularis propria 268 287 ICecum 6.5 T2 G2 Invades full thickness of muscularis propria, butmesenteric adipose free of malignancy 278 297 III Rectum 4 T3 G2Invasion into perirectal adipose tissue. 295 314 II Ascending 5.0 T3 G2Invasion through colon muscularis propria into percolic adipose tissue.296 315 III Cecum 5.5 T3 G2 Invasion through muscularis propria andinvades pericolic adipose tissue. Ileocecal junction. 300 319 IIIDescending 5.2 T2 G2 through the colon muscularis propria into pericolicfat 322 341 II Sigmoid 7 T3 G2 through the muscularis propria intopericolic fat 339 358 II Rectosigmoid 6 T3 G2 Extends into perirectalfat but does not reach serosa 341 360 II Ascending 2 cm T3 G2 Invasionthrough colon invasive muscularis propria to involve pericolonic fat.Arising from villous adenoma. 356 375 II Sigmoid 6.5 T3 G2 Through colonwall into subserosal adipose tissue. No serosal spread seen. 360 412 IIIAscending 4.3 T3 G2 Invasion thru colon muscularis propria topericolonic fat 392 444 IV Ascending 2 T3 G2 Invasion through colonmuscularis propria into subserosal adipose tissue, not serosa. 393 445II Cecum 6.0 T3 G2 Cecum, invades through muscularis propria to involvesubserosal adipose tissue but not serosa. 413 465 IV Cecum 4.8 T3 G2Invasive through muscularis to involve periserosal fat; abuttingileocecal junction. 452 504 II Ascending 4 T3 G2 through colonmuscularis propria approaching pericolic fat, but not at serosal surface505 383 IV 7.5 T3 G2 Invasion through muscularis propria involvingpericolic adipose, serosal surface uninvolved 517 395 IV Sigmoid 3 T3 G2penetrates muscularis propria, involves pericolonic fat. 534 553 IIAscending 12 T3 G3 Invasion through colon the muscularis propriainvolving pericolic fat. Serosa free of tumor. 546 565 IV Ascending 5.5T3 G2 Invasion through colon muscularis propria extensively throughsubmucosal and extending to serosa. 577 596 II Cecum 11.5 T3 G2 Invasionthrough the bowel wall, into suberosal adipose. Serosal surface free oftumor. 695 714 II Cecum 14.0 T3 G2 extending through bowel wall intoserosal fat 784 803 IV Ascending 3.5 T3 G3 through colon muscularispropria into pericolic soft tissues 786 805 IV Descending 9.5 T3 G2through colon muscularis propria into pericolic fat, but not at serosalsurface 787 806 II Rectosigmoid 2.5 T3 G2-G3 Invasion of muscularispropria into soft tissue 789 808 IV Cecum 5.0 T3 G2-G3 Extending throughmuscularis propria into pericolonic fat 790 809 IV Rectum 6.8 T3 G1-G2Invading through muscularis propria into perirectal fat 791 810 IVAscending 5.8 T3 G3 Through the colon muscularis propria into pericolicfat 888 908 IV Ascending 2.0 T2 G1 Into muscularis colon propria 889 909IV Cecum 4.8 T3 G2 Through muscularis propria int subserosal tissue 890910 IV Ascending T3 G2 Through colon muscularis propria into subserosa.891 911 IV Rectum 5.2 T3 G2 Invasion through muscularis propria intoperirectal soft tissue 892 912 IV Sigmoid 5.0 T3 G2 Invasion intopericolic sort tissue. Tumor focally invading skeletal muscle attachedto colon. 893 913 IV Transverse 6.0 T3 G2-G3 Through colon muscularispropria into pericolic fat 989 1009 IV Sigmoid 6.0 T3 G2 Invasionthrough colon wall and focally involving subserosal tissue. Lymph RegDist Lymph Met Lymph Dist Met Met Pt ID Met Incid Grade & Loc GradeComment  10 Pos 1/17 N1 Neg M0 Moderately differentiated  15 Pos 3/8  N1Neg MX invasive adenocarcinoma, moderately differentiated; focalperineural invasion is seen  52 Neg 0/12 N0 Neg M0 Hyperplastic polyp inappendix. 121 Neg 0/34 N0 Neg M0 Perineural invasion; donut anastomosisNeg. One tubulovillous and one tubular adenoma with no high gradedysplasia. 125 Neg 0/19 N0 Neg M0 patient history of metastatic melanoma128 Pos 1/5  N1 Neg M0 130 Pos 10/24  N2 Neg M1 133 Neg 0/9  N0 Neg M0Small separate tubular adenoma (0.4 cm) 141 Pos 7/21 N2 Pos - M1Perineural Liver invasion identified adjacent to metastaticadenocarcinoma. 156 Pos 2/13 N1 Neg M0 Separate tubolovillous andtubular adenomas 228 Pos 1/8  N1 Neg MX Hyperplastic polyps 264 Neg 0/10N0 Neg M0 Tubulovillous adenoma with high grade dysplasia 266 Neg 0/15N1 Pos - MX Mesenteric deposit 267 Pos 2/12 N1 Neg M0 268 Neg 0/12 N0Neg M0 278 Pos 7/10 N2 Neg M0 Descending colon polyps, no HGD orcarcinoma identified.. 295 Neg 0/12 N0 Neg M0 Melanosis coli anddiverticular disease. 296 Pos 2/12 N1 Neg M0 Tubulovillous adenoma (2.0cm) with no high grade dysplasia. Neg. liver biopsy. 300 Pos 2/2  N1 NegM0 322 Neg 0/5  N0 Neg M0 vascular invasion is identified 339 Neg 0/6 N0 Neg M0 1 hyperplastic polyp identified 341 Neg 0/4  N0 Neg MX 356 Neg0/4  N0 Neg M0 360 Pos 1/5  N1 Neg M0 Two mucosal polyps 392 Pos 1/6  N1Pos - M1 Tumor arising Liver at prior ileocolic surgical anastomosis.393 Neg 0/21 N0 Neg M0 413 Neg 0/7  N0 Pos - M1 rediagnosis of Liveroophorectomy path to metastatic colon cancer. 452 Neg 0/39 N0 Neg M0 505Pos 2/17 N1 Pos - M1 Anatomical Liver location of primary not notated inreport. Evidence of chronic colitis. 517 Pos 6/6  N2 Neg M0 No mentionof distant met in report 534 Neg 0/8  N0 Neg M0 Omentum with fibrosisand fat necrosis. Small bowel with acute and chronic serositis, focalabscess and adhesions. 546 Pos 6/12 N2 Pos - M1 Liver 577 Neg 0/58 N0Neg M0 Appendix dilated and fibrotic, but not involved by tumor 695 Neg0/22 N0 Neg MX moderately differentiated adenocarcinoma with mucinousdiferentiation (% not stated), tubular adenoma and hyperplstic polypspresent, 784 Pos 5/17 N2 Pos - M1 invasive poorly Liver differentiatedadenosquamous carcinoma 786 Neg 0/12 N0 Pos - M1 moderately Liverdifferentiated invasive adenocarcinoma 787 Neg N0 Neg MX Peritumorallymphocytic response; 5 LN examined in pericolic fat, no metastatasesobserved. 789 Pos 5/10 N2 Pos - M1 Three fungating Liver lesionsexamined. 790 Pos 3/13 N1 Pos - M1 Liver 791 Pos 13/25  N2 Pos - M1poorly Liver differentiated invasive colonic adenocarcinoma 888 Pos 3/21N0 Pos - M1 well to Liver moderately differentiated adenocarcinomas;this patient has tumors of the ascending colon and the sigmoid colon 889Pos 1/4  N1 Pos - M1 moderately Liver differentiated adenocarcinoma 890Pos 11/15  N2 Pos - M1 Liver 891 Pos 4/15 N2 Pos - M1 Perineural Liverinvasion present. 892 Pos 1/28 N1 Pos - M1 Perineural Liver, leftinvasion and right present, lobe, extensive. omentum Patient with ahistory of colon cancer. 893 Pos 14/17  N2 Pos - M1 Perineural Liverinvasion focally present. Omentum mass, but resection with no tumoridentified. 989 Pos 1/7  N1 Pos - M1 Primary Liver adenocarcinomaarising from tubulovillous adenoma.

Two overlapping groups of patients described in Table 34 were studied.The first group contained 33 members whereas the second group contained22 members. In the case of the first group of patients, gene productexpression profiles of tissue samples from metastasized tumors werecompared to gene product expression profiles of an “unmatched” sample,where the unmatched sample is a pool of samples of normal colon from thesample patients. For the second group of patients, gene productexpression profiles of tissue samples from metastasized tumors werecompared to gene product expression profiles of a “matched” sample,where the matched sample is matched to a single sample within a patient.As such, a metastasized colon tumor sample is “matched” with a normalcolon sample or a primary colon tumor from the same patient. Metastasesof colon cancers may appear in any tissue, including bone, breast, lung,liver, brain, kidney skin, intestine, appendix, etc. In many patients,the colon cancer had metastasized to liver.

Source of Polynucleotides on Arrays

Polynucleotides for use on the arrays were obtained from both publiclyavailable sources and from cDNA libraries generated from selected celllines and patient tissues. Table 35 provides information about thepolynucleotides on the arrays including: (1) the “SEQ ID NO” assigned toeach sequence for use in the present specification; (2) the spotidentification number (“Spot ID”), an internal reference that serves asa unique identifier for the spot on the array; (3) the “Clone ID”assigned to the clone from which the sequence was isolated; and (4) the“MAClone ID” assigned to the clone from which the sequence was isolated.The sequences corresponding to the SEQ ID NOS are provided in theSequence Listing.

Characterization of Sequences

The sequences of the isolated polynucleotides were first masked toeliminate low complexity sequences using the RepeatMasker maskingprogram, publicly available through a web site supported by theUniversity of Washington (See also Smit, A. F. A. and Green, P.,unpublished results). Generally, masking does not influence the finalsearch results, except to eliminate sequences of relatively littleinterest due to their low complexity, and to eliminate multiple “hits”based on similarity to repetitive regions common to multiple sequences,e.g., Alu repeats. Masking resulted in the elimination of severalsequences.

The remaining sequences of the isolated polynucleotides were used in ahomology search of the GenBank database using the TeraBLAST program(TimeLogic, Crystal Bay, Nev.), a DNA and protein sequence homologysearching algorithm. TeraBLAST is a version of the publicly availableBLAST search algorithm developed by the National Center forBiotechnology, modified to operate at an accelerated speed withincreased sensitivity on a specialized computer hardware platform. Theprogram was run with the default parameters recommended by TimeLogic toprovide the best sensitivity and speed for searching DNA and proteinsequences. Gene assignment for the query sequences was determined basedon best hit from the GenBank database; expectancy values are providedwith the hit.

Summary of TeraBLAST Search Results

Table 36 provides information about the gene corresponding to eachpolynucleotide. Table 36 includes: (1) the “SEQ ID NO” of the sequence;(2) the “Clone ID” assigned to the clone from which the sequence wasisolated; (3) the “MAClone ID” assigned to the clone from which thesequence was isolated; (4) the library source of the clone(“PatientType”); (5) the GenBank Accession Number of the publiclyavailable sequence corresponding to the polynucleotide (“GBHit”); (6) adescription of the GenBank sequence (“GBDescription”); and (7) the scoreof the similarity of the polynucleotide sequence and the GenBanksequence (“GBScore”). The published information for each GenBank and ESTdescription, as well as the corresponding sequence identified by theprovided accession number, are incorporated herein by reference.

Example 59 Detection of Differential Expression Using Arrays

cDNA probes were prepared from total RNA isolated from the patientsamples described above. Since LCM provides for the isolation ofspecific cell types to provide a substantially homogenous cell sample,this provided for a similarly pure RNA sample.

Total RNA was first reverse transcribed into cDNA using a primercontaining a T7 RNA polymerase promoter, followed by second strand DNAsynthesis. cDNA was then transcribed in vitro to produce antisense RNAusing the T7 promoter-mediated expression (see, e.g., Luo et al. (1999)Nature Med 5:117-122), and the antisense RNA was then converted intocDNA. The second set of cDNAs were again transcribed in vitro, using theT7 promoter, to provide antisense RNA. Optionally, the RNA was againconverted into cDNA, allowing for up to a third round of T7-mediatedamplification to produce more antisense RNA. Thus the procedure providedfor two or three rounds of in vitro transcription to produce the finalRNA used for fluorescent labeling.

Fluorescent probes were generated by first adding control RNA to theantisense RNA mix, and producing fluorescently labeled cDNA from the RNAstarting material. Fluorescently labeled cDNAs prepared from the tumorRNA sample were compared to fluorescently labeled cDNAs prepared from anormal cell RNA sample. For example, the cDNA probes from the normalcells were labeled with Cy3 fluorescent dye (green) and the cDNA probesprepared from the tumor cells were labeled with Cy5 fluorescent dye(red), and vice versa.

Each array used had an identical spatial layout and control spot set.Each microarray was divided into two areas, each area having an arraywith, on each half, twelve groupings of 32×12 spots, for a total ofabout 9,216 spots on each array. The two areas are spotted identicallywhich provides for at least two duplicates of each clone per array.

Polynucleotides for use on the arrays were obtained from both publiclyavailable sources and from cDNA libraries generated from selected celllines and patient tissues as described above and in Table 35. PCRproducts of from about 0.5 kb to 2.0 kb amplified from these sourceswere spotted onto the array using a Molecular Dynamics Gen III spotteraccording to the manufacturer's recommendations. The first row of eachof the 24 regions on the array had about 32 control spots, including 4negative control spots and 8 test polynucleotides. The testpolynucleotides were spiked into each sample before the labelingreaction with a range of concentrations from 2-600 pg/slide and ratiosof 1:1. For each array design, two slides were hybridized with the testsamples reverse-labeled in the labeling reaction. This provided forabout four duplicate measurements for each clone, two of one color andtwo of the other, for each sample.

The differential expression assay was performed by mixing equal amountsof probes from matched or unmatched samples. The arrays werepre-incubated for about 2 hrs at 60° C. in 5×SSC/0.2% SDS/1 mM EDTA, andthen washed three times in water and twice in isopropanol. Followingprehybridization of the array, the probe mixture was then hybridized tothe array under conditions of high stringency (overnight at 42° C. in50% formamide, 5×SSC, and 0.2% SDS. After hybridization, the array waswashed at 55° C. three times as follows: 1) first wash in 1×SSC/0.2%SDS; 2) second wash in 0.1×SSC/0.2% SDS; and 3) third wash in 0.1×SSC.

The arrays were then scanned for green and red fluorescence using aMolecular Dynamics Generation III dual color laser-scanner/detector. Theimages were processed using BioDiscovery Autogene software, and the datafrom each scan set normalized to provide for a ratio of expressionrelative to normal. Data from the microarray experiments was analyzedaccording to the algorithms described in U.S. application Ser. No.60/252,358, filed Nov. 20, 2000, by E. J. Moler, M. A. Boyle, and F. M.Randazzo, and entitled “Precision and accuracy in cDNA microarray data,”which application is specifically incorporated herein by reference.

The experiment was repeated, this time labeling the two probes with theopposite color in order to perform the assay in both “color directions.”Each experiment was sometimes repeated with two more slides (one in eachcolor direction). The level of fluorescence for each sequence on thearray expressed as a ratio of the geometric mean of 8 replicatespots/genes from the four arrays or 4 replicate spots/gene from 2 arraysor some other permutation. The data were normalized using the spikedpositive controls present in each duplicated area, and the precision ofthis normalization was included in the final determination of thesignificance of each differential. The fluorescent intensity of eachspot was also compared to the negative controls in each duplicated areato determine which spots have detected significant expression levels ineach sample.

A statistical analysis of the fluorescent intensities was applied toeach set of duplicate spots to assess the precision and significance ofeach differential measurement, resulting in a p-value testing the nullhypothesis that there is no differential in the expression level betweenthe tumor and normal samples of each patient. During initial analysis ofthe microarrays, the hypothesis was accepted if p>10⁻³, and thedifferential ratio was set to 1.000 for those spots. All other spotshave a significant difference in expression between the matched orunmatched samples. If the tumor sample has detectable expression and thenormal does not, the ratio is truncated at 1000 since the value forexpression in the normal sample would be zero, and the ratio would notbe a mathematically useful value (e.g., infinity). If the normal samplehas detectable expression and the tumor does not, the ratio is truncatedto 0.001, since the value for expression in the tumor sample would bezero and the ratio would not be a mathematically useful value. Theselatter two situations are referred to herein as “on/off.” Databasetables were populated using a 95% confidence level (p>0.05).

Table 37 provides the results for gene products that were over- orunder-expressed as determined by comparison of matched or unmatchedpairs of samples isolated from the two patient groups described above.The results show data from three separate experiments using the same setof gene products, each identified by SEQ ID NO. The three experimentsare: 1) a comparison of the gene expression profile of metastasizedcolon tumor tissue compared to unmatched normal colon tissue (“unmatchedmetastasis/normal”); 2) a comparison of the gene expression profile ofmetastasized colon tumor tissue compared to normal colon tissue from thesame patient (“matched metastasis/normal”); and 3) a comparison of thegene expression profile of metastasized colon tumor tissue compared toprimary tumor tissue from the same patient (“matched metastasis/tumor”).If samples are matched, they are both samples from a single patient. Ifsamples are unmatched, one sample is obtained from a patient, andcompared to pooled samples from many patients.

The results in Table 37 show the sequences that are induced by at least2-fold or greater in the metastasized colon tumor samples relative tonormal or primary tumor tissue samples in at least 20% of the patientstested, or gene products in which expression levels of the gene inmetastasized colon tumor cells was less than or equal to ½ of theexpression level in normal or primary tissue samples in at least 20% ofthe patients tested. Table 37 Table 35 includes: (1) the “SEQ ID NO” ofthe sequence tested; (2) the “Clone ID” assigned to the clone from whichthe sequence was isolated; and (3) the “MAClone ID” assigned to theclone from which the sequence was isolated; (4) the percentage ofpatients tested in which expression levels (e.g., as message level) of aparticular sequence was at least 2-fold greater in metastasized coloncancer tissue than in unmatched or matched colon tissue (“>=2×”); (5)the percentage of patients tested in which expression levels (e.g., asmessage level) of the gene was less than or equal to ½ of the expressionlevel in matched or unmatched colon tissue (“<=half×”); and (6) thenumber of patients analyzed in each experiment (“Ratios”).

These data provide evidence that the genes represented by thepolynucleotides having the indicated sequences are differentiallyexpressed in colon cancer, particularly metastasized colon cancer, ascompared to colon cancer primary tumors or normal non-cancerous colontissue.

Example 60 Antisense Regulation of Gene Expression

The expression of the differentially expressed genes represented by thepolynucleotides in the cancerous cells can be analyzed using antisenseknockout technology to confirm the role and function of the gene productin tumorigenesis, e.g., in promoting a metastatic phenotype.

A number of different oligonucleotides complementary to the mRNAgenerated by the differentially expressed genes identified herein can bedesigned as potential antisense oligonucleotides, and tested for theirability to suppress expression of the genes. Sets of antisense oligomersspecific to each candidate target are designed using the sequences ofthe polynucleotides corresponding to a differentially expressed gene andthe software program HYB simulator Version 4 (available for Windows95/Windows NT or for Power Macintosh, RNAture, Inc. 1003 Health SciencesRoad, West, Irvine, Calif. 92612 USA). Factors that are considered whendesigning antisense oligonucleotides include: 1) the secondary structureof oligonucleotides; 2) the secondary structure of the target gene; 3)the specificity with no or minimum cross-hybridization to otherexpressed genes; 4) stability; 5) length and 6) terminal GC content. Theantisense oligonucleotide is designed so that it will hybridize to itstarget sequence under conditions of high stringency at physiologicaltemperatures (e.g., an optimal temperature for the cells in culture toprovide for hybridization in the cell, e.g., about 37° C.), but withminimal formation of homodimers.

Using the sets of oligomers and the HYB simulator program, three to tenantisense oligonucleotides and their reverse controls are designed andsynthesized for each candidate mRNA transcript, which transcript isobtained from the gene corresponding to the target polynucleotidesequence of interest. Once synthesized and quantitated, the oligomersare screened for efficiency of a transcript knock-out in a panel ofcancer cell lines. The efficiency of the knock-out is determined byanalyzing mRNA levels using lightcycler quantification. The oligomersthat resulted in the highest level of transcript knock-out, wherein thelevel was at least about 50%, preferably about 80-90%, up to 95% or moreup to undetectable message, are selected for use in a cell-basedproliferation assay, an anchorage independent growth assay, and anapoptosis assay.

The ability of each designed antisense oligonucleotide to inhibit geneexpression is tested through transfection into SW620 colon carcinomacells. For each transfection mixture, a carrier molecule (such as alipid, lipid derivative, lipid-like molecule, cholesterol, cholesterolderivative, or cholesterol-like molecule) is prepared to a workingconcentration of 0.5 mM in water, sonicated to yield a uniform solution,and filtered through a 0.45 μm PVDF membrane. The antisense or controloligonucleotide is then prepared to a working concentration of 100 μM insterile Millipore water. The oligonucleotide is further diluted inOptiMEM™ (Gibco/BRL), in a microfuge tube, to 2 or approximately 20 μgoligo/ml of OptiMEM™. In a separate microfuge tube, the carriermolecule, typically in the amount of about 1.5-2 nmol carrier/μgantisense oligonucleotide, is diluted into the same volume of OptiMEM™used to dilute the oligonucleotide. The diluted antisenseoligonucleotide is immediately added to the diluted carrier and mixed bypipetting up and down. Oligonucleotide is added to the cells to a finalconcentration of 30 nM.

The level of target mRNA that corresponds to a target gene of interestin the transfected cells is quantitated in the cancer cell lines usingthe Roche LightCycler™ real-time PCR machine. Values for the target mRNAare normalized versus an internal control (e.g., beta-actin). For each20 μl reaction, extracted RNA (generally 0.2-1 μg total) is placed intoa sterile 0.5 or 1.5 ml microcentrifuge tube, and water is added to atotal volume of 12.5 μl. To each tube is added 7.5 μl of a buffer/enzymemixture, prepared by mixing (in the order listed) 2.5 μl H₂O, 2.0 μl 10×reaction buffer, 10 μl oligo dT (20 μmol), 1.0 μl dNTP mix (10 mM each),0.5 μl RNAsin® (20 u) (Ambion, Inc., Hialeah, Fla.), and 0.5 μl MMLVreverse transcriptase (50 u) (Ambion, Inc.). The contents are mixed bypipetting up and down, and the reaction mixture is incubated at 42° C.for 1 hour. The contents of each tube are centrifuged prior toamplification.

An amplification mixture is prepared by mixing in the following order:1×PCR buffer II, 3 mM MgCl₂, 140 μM each dNTP, 0.175 μmol each oligo,1:50,000 dil of SYBR® Green, 0.25 mg/ml BSA, 1 unit Taq polymerase, andH₂O to 20 (PCR buffer II is available in 10× concentration fromPerkin-Elmer, Norwalk, Conn.). In 1× concentration it contains 10 mMTris pH 8.3 and 50 mM KCl. SYBR® Green (Molecular Probes, Eugene, Oreg.)is a dye which fluoresces when bound to double stranded DNA. As doublestranded PCR product is produced during amplification, the fluorescencefrom SYBR® Green increases. To each 20 μl aliquot of amplificationmixture, 2 μl of template RT is added, and amplification is carried outaccording to standard protocols. The results are expressed as thepercent decrease in expression of the corresponding gene productrelative to non-transfected cells, vehicle-only transfected(mock-transfected) cells, or cells transfected with reverse controloligonucleotides.

Example 61 Effect of Expression on Proliferation

The effect of gene expression on the inhibition of cell proliferationcan be assessed in, for example, metastatic breast cancer cell lines(MDA-MB-231 (“231”)); SW620 colon colorectal carcinoma cells; SKOV3cells (a human ovarian carcinoma cell line); or LNCaP, PC3, 22Rv1,MDA-PCA-2b, or DU145 prostate cancer cells.

Cells are plated to approximately 60-80% confluency in 96-well dishes.Antisense or reverse control oligonucleotide is diluted to 2 μM inOptiMEM™. The oligonucleotide-OptiMEM™ can then be added to a deliveryvehicle, which delivery vehicle can be selected so as to be optimizedfor the particular cell type to be used in the assay. The oligo/deliveryvehicle mixture is then further diluted into medium with serum on thecells. The final concentration of oligonucleotide for all experimentscan be about 300 nM.

Antisense oligonucleotides are prepared as described above (see Example60). Cells are transfected overnight at 37° C. and the transfectionmixture is replaced with fresh medium the next morning. Transfection iscarried out as described above in Example 60.

Those antisense oligonucleotides inhibit proliferation of SW620 cellsindicate that the corresponding gene plays a role in production ormaintenance of the cancerous phenotype in cancerous colon cells. Thoseantisense oligonucleotides that inhibit proliferation in SKOV3 cellsrepresent genes that play a role in production or maintenance of thecancerous phenotype in cancerous breast cells. Those antisenseoligonucleotides that result in inhibition of proliferation ofMDA-MB-231 cells indicate that the corresponding gene plays a role inproduction or maintenance of the cancerous phenotype in cancerousovarian cells. Those antisense oligonucleotides that inhibitproliferation in LNCaP, PC3, 22Rv1, MDA-PCA-2b, or DU145 cells representgenes that play a role in production or maintenance of the cancerousphenotype in cancerous prostate cells.

Example 62 Effect of Gene Expression on Cell Migration

The effect of gene expression on the inhibition of cell migration can beassessed in SW620 colon cancer cells using static endothelial cellbinding assays, non-static endothelial cell binding assays, andtransmigration assays.

For the static endothelial cell binding assay, antisenseoligonucleotides are prepared as described above (see Example 60). Twodays prior to use, colon cancer cells (CaP) are plated and transfectedwith antisense oligonucleotide as described above (see Examples 60 and61). On the day before use, the medium is replaced with fresh medium,and on the day of use, the medium is replaced with fresh mediumcontaining 2 μM CellTracker green CMFDA (Molecular Probes, Inc.) andcells are incubated for 30 min. Following incubation, CaP medium isreplaced with fresh medium (no CMFDA) and cells are incubated for anadditional 30-60 min. CaP cells are detached using CMF PBS/2.5 mM EDTAor trypsin, spun and resuspended in DMEM/1% BSA/10 mM HEPES pH 7.0.Finally, CaP cells are counted and resuspended at a concentration of1×10⁶ cells/ml.

Endothelial cells (EC) are plated onto 96-well plates at 40-50%confluence 3 days prior to use. On the day of use, EC are washed 1× withPBS and 50λ DMDM/1% BSA/10 mM HEPES pH 7 is added to each well. To eachwell is then added 50K (50□) CaP cells in DMEM/1% BSA/10 mM HEPES pH 7.The plates are incubated for an additional 30 min and washed 5× with PBScontaining Ca⁺⁺ and Mg⁺⁺. After the final wash, 100 μL PBS is added toeach well and fluorescence is read on a fluorescent plate reader(Ab492/Em 516 nm).

For the non-static endothelial cell binding assay, CaP are prepared asdescribed above. EC are plated onto 24-well plates at 30-40% confluence3 days prior to use. On the day of use, a subset of EC are treated withcytokine for 6 hours then washed 2× with PBS. To each well is then added150-200K CaP cells in DMEM/1% BSA/10 mM HEPES pH 7. Plates are placed ona rotating shaker (70 RPM) for 30 min and then washed 3× with PBScontaining Ca⁺⁺ and Mg⁺⁺. After the final wash, 500 μL PBS is added toeach well and fluorescence is read on a fluorescent plate reader(Ab492/Em 516 nm).

For the transmigration assay, CaP are prepared as described above withthe following changes. On the day of use, CaP medium is replaced withfresh medium containing 5 μM CellTracker green CMFDA (Molecular Probes,Inc.) and cells are incubated for 30 min. Following incubation, CaPmedium is replaced with fresh medium (no CMFDA) and cells are incubatedfor an additional 30-60 min. CaP cells are detached using CMF PBS/2.5 mMEDTA or trypsin, spun and resuspended in EGM-2-MV medium. Finally, CaPcells are counted and resuspended at a concentration of 1×106 cells/ml.

EC are plated onto FluorBlok transwells (BD Biosciences) at 30-40%confluence 5-7 days before use. Medium is replaced with fresh medium 3days before use and on the day of use. To each transwell is then added50K labeled CaP. 30 min prior to the first fluorescence reading, 10 μgof FITC-dextran (10K MW) is added to the EC plated filter. Fluorescenceis then read at multiple time points on a fluorescent plate reader(Ab492/Em 516 nm).

Those antisense oligonucleotides that result in inhibition of binding ofSW620 colon cancer cells to endothelial cells indicate that thecorresponding gene plays a role in the production or maintenance of thecancerous phenotype in cancerous colon cells. Those antisenseoligonucleotides that result in inhibition of endothelial celltransmigration by SW620 colon cancer cells indicate that thecorresponding gene plays a role in the production or maintenance of thecancerous phenotype in cancerous colon cells.

Example 63 Effect of Gene Expression on Colony Formation

The effect of gene expression upon colony formation of SW620 cells,SKOV3 cells, MD-MBA-231 cells, LNCaP cells, PC3 cells, 22Rv1 cells,MDA-PCA-2b cells, and DU145 cells can be tested in a soft agar assay.Soft agar assays are conducted by first establishing a bottom layer of 2ml of 0.6% agar in media plated fresh within a few hours of layering onthe cells. The cell layer is formed on the bottom layer by removingcells transfected as described above from plates using 0.05% trypsin andwashing twice in media. The cells are counted in a Coulter counter, andresuspended to 10⁶ per ml in media. 10 μl aliquots are placed with mediain 96-well plates (to check counting with WST1), or diluted further forthe soft agar assay. 2000 cells are plated in 800 μl 0.4% agar induplicate wells above 0.6% agar bottom layer. After the cell layer agarsolidifies, 2 ml of media is dribbled on top and antisense or reversecontrol oligo (produced as described in Example 60) is added withoutdelivery vehicles. Fresh media and oligos are added every 3-4 days.Colonies form in 10 days to 3 weeks. Fields of colonies are counted byeye. WST-1 metabolism values can be used to compensate for smalldifferences in starting cell number. Larger fields can be scanned forvisual record of differences.

Those antisense oligonucleotides that result in inhibition of colonyformation of SW620 cells indicate that the corresponding gene plays arole in production or maintenance of the cancerous phenotype incancerous colon cells. Those antisense oligonucleotides that inhibitcolony formation in SKOV3 cells represent genes that play a role inproduction or maintenance of the cancerous phenotype in cancerous breastcells. Those antisense oligonucleotides that result in inhibition ofcolony formation of MDA-MB-231 cells indicate that the correspondinggene plays a role in production or maintenance of the cancerousphenotype in cancerous ovarian cells. Those antisense oligonucleotidesthat inhibit colony formation in LNCaP, PC3, 22Rv1, MDA-PCA-2b, or DU145cells represent genes that play a role in production or maintenance ofthe cancerous phenotype in cancerous prostate cells.

Example 64 Induction of Cell Death Upon Depletion of Polypeptides byDepletion of mRNA (“Antisense Knockout”)

In order to assess the effect of depletion of a target message upon celldeath, SW620 cells, or other cells derived from a cancer of interest,can be transfected for proliferation assays. For cytotoxic effect in thepresence of cisplatin (cis), the same protocol is followed but cells areleft in the presence of 2 μM drug. Each day, cytotoxicity is monitoredby measuring the amount of LDH enzyme released in the medium due tomembrane damage. The activity of LDH is measured using the CytotoxicityDetection Kit from Roche Molecular Biochemicals. The data is provided asa ratio of LDH released in the medium vs. the total LDH present in thewell at the same time point and treatment (rLDH/tLDH). A positivecontrol using antisense and reverse control oligonucleotides for BCL2 (aknown anti-apoptotic gene) is included; loss of message for BCL2 leadsto an increase in cell death compared with treatment with the controloligonucleotide (background cytotoxicity due to transfection).

Example 65 Reduction of Colon Cancer In Vivo

In order to assess the effect of depletion of a target message uponcolon cancer metastasis and the growth of metastasized colon cancercells in vivo, a mouse model is utilized. Mouse models for cancermetastasis are well known in the art (e.g. Hubbard et al Dis ColonRectum. 2002 45:334-41; Rashidi et al Clin Cancer Res. 2000 6:2556-61;Rashidi et al Anticancer Res. 2000 20:715-22; Rho et al Anticancer Res.1999 19:157-61; Hasegawa et al, Int J Cancer 1998 76:812-6; and Warrenet al J Clin Invest. 1995 95:1789-97.

In one model, before, at the same time as, or sometime after theintravenous or intraperitoneal administration of cancer cells to a modelmouse, antisense molecules of Example 60 or other inhibitory moleculesare administered to the model mouse. Cancer progression, includingestablishment and growth of tumors derived from the administered cellsand longevity of mice, are monitored.

Example 66 Functional Analysis of Gene Products Differentially Expressedin Colon Cancer in Patients

The gene products of sequences of a gene differentially expressed incancerous cells can be further analyzed to confirm the role and functionof the gene product in tumorigenesis, e.g., in promoting or inhibitingdevelopment of a metastatic phenotype. For example, the function of geneproducts corresponding to genes identified herein can be assessed byblocking function of the gene products in the cell. For example, wherethe gene product is secreted or associated with a cell surface membrane,blocking antibodies can be generated and added to cells to examine theeffect upon the cell phenotype in the context of, for example, thetransformation of the cell to a cancerous, particularly a metastatic,phenotype. In order to generate antibodies, a clone corresponding to aselected gene product is selected, and a sequence that represents apartial or complete coding sequence is obtained. The resulting clone isexpressed, the polypeptide produced isolated, and antibodies generated.The antibodies are then combined with cells and the effect upontumorigenesis assessed.

Where the gene product of the differentially expressed genes identifiedherein exhibits sequence homology to a protein of known function (e.g.,to a specific kinase or protease) and/or to a protein family of knownfunction (e.g., contains a domain or other consensus sequence present ina protease family or in a kinase family), then the role of the geneproduct in tumorigenesis, as well as the activity of the gene product,can be examined using small molecules that inhibit or enhance functionof the corresponding protein or protein family.

Additional functional assays include, but are not necessarily limitedto, those that analyze the effect of expression of the correspondinggene upon cell cycle and cell migration. Methods for performing suchassays are well known in the art.

Example 67 Contig Assembly and Additional Gene Characterization

The sequences of the polynucleotides provided in the present inventioncan be used to extend the sequence information of the gene to which thepolynucleotides correspond (e.g., a gene, or mRNA encoded by the gene,having a sequence of the polynucleotide described herein). This expandedsequence information can in turn be used to further characterize thecorresponding gene, which in turn provides additional information aboutthe nature of the gene product (e.g., the normal function of the geneproduct). The additional information can serve to provide additionalevidence of the gene product's use as a therapeutic target, and providefurther guidance as to the types of agents that can modulate itsactivity.

In one example, a contig is assembled using a sequence of apolynucleotide of the present invention, which is present in a clone. A“contig” is a contiguous sequence of nucleotides that is assembled fromnucleic acid sequences having overlapping (e.g., shared or substantiallysimilar) sequence information. The sequences of publicly-available ESTs(Expressed Sequence Tags) and the sequences of various clones fromseveral cDNA libraries synthesized at Chiron can be used in the contigassembly.

The contig is assembled using the software program Sequencher, version4.05, according to the manufacturer's instructions and an overviewalignment of the contiged sequences is produced. The sequenceinformation obtained in the contig assembly can then be used to obtain aconsensus sequence derived from the contig using the Sequencher program.The consensus sequence is used as a query sequence in a TeraBLASTNsearch of the DGTI DoubleTwist Gene Index (DoubleTwist, Inc., Oakland,Calif.), which contains all the EST and non-redundant sequence in publicdatabases.

Through contig assembly and the use of homology searching softwareprograms, the sequence information provided herein can be readilyextended to confirm, or confirm a predicted, gene having the sequence ofthe polynucleotides described in the present invention. Further theinformation obtained can be used to identify the function of the geneproduct of the gene corresponding to the polynucleotides describedherein. While not necessary to the practice of the invention,identification of the function of the corresponding gene, can provideguidance in the design of therapeutics that target the gene to modulateits activity and modulate the cancerous phenotype (e.g., inhibitmetastasis, proliferation, and the like).

While the present invention has been described with reference to thespecific embodiments thereof, it should be understood by those skilledin the art that various changes may be made and equivalents may besubstituted without departing from the true spirit and scope of theinvention. In addition, many modifications may be made to adapt aparticular situation, material, composition of matter, process, processstep or steps, to the objective, spirit and scope of the presentinvention. All such modifications are intended to be within the scope ofthe claims appended hereto.

1. A method for detecting a cancerous cell, said method comprising:detecting a level of a product of a nucleic acid comprising SEQ ID NO:9228 in a test sample obtained from a cell of a subject, comparing thelevel of said gene product to a control level of said gene product,wherein the presence of a cancerous cell is indicated by detection ofsaid level and comparison to said control level.
 2. The method of claim1, wherein said cancerous cell is a cancerous breast cell.
 3. The methodof claim 1, wherein said gene product is nucleic acid.
 4. The method ofclaim 1, wherein said gene product is a polypeptide comprising the aminoacid sequence encoded by SEQ ID NO:
 9228. 5. The method of claim 1,wherein said detecting step comprises a polymerase chain reaction. 6.The method of claim 1, wherein said detecting step uses compriseshybridization.
 7. The method of claim 1, wherein said sample is a sampleof breast tissue.
 8. The method of claim 1, wherein said level of saidproduct is indicative of the cancerous state of the cell of the testsample.
 9. The method of claim 1, wherein said cancerous cell is acancerous colon cell.
 10. A method for assessing the tumor burden of asubject, said method comprising: detecting a level of a product of anucleic acid comprising SEQ ID NO: 9228 in a test sample from a subject,wherein the level of said gene product in the test sample is indicativeof the tumor burden in the subject.
 11. The method of claim 10, whereinsaid cancerous cell is a cancerous colon cell.